gebhart/patrepeval huggingface dataset:
Distributions of enzyme residues yielding mutants with improved substrate specificities from two different directed evolution strategies (2009)

A previous study of random mutations, mostly introduced by error-prone PCR (EPPCR) or DNA shuffling (DS), demonstrated that those closer to the enzyme active site were more effective than distant ones at improving enzyme activity, substrate specificity or enantioselectivity. Since then, many studies have taken advantage of this observation by targeting site-directed saturation mutagenesis (SDSM) to residues closer to or within enzyme active sites. Here, we have analysed a set of SDSM studies, in parallel to a similar set from EPPCR/DS, to determine whether the greater range of amino-acid types accessible by SDSM affects the distances at which the most effective sites occur. We have also analysed the relative effectiveness for obtaining beneficial mutants of residues with different degrees of natural sequence variation, as determined by their sequence entropy which is related to sequence conservation. These analyses attempt to answer the question-how well focused have targeted mutagenesis strategies been? We also compared two different sets of active-site atoms from which to measure distances and found that the inclusion of catalytic, substrate and cofactor atoms refined the analysis compared to using a single key catalytic atom. Using this definition, we found that EPPCR/DS is not effective for altering substrate specificity at sites that are within 5 A of the active-site atoms. In contrast, SDSM is most effective when targeted to residues at <5-6 A from the catalytic, substrate or cofactor atom, and also for residues with intermediate sequence entropies. Furthermore, SDSM is capable of altering substrate specificity at highly and completely conserved residues in the active site. The results suggest ways in which directed evolution by SDSM could be improved for greater efficiency in terms of reducing the library sizes required to obtain beneficial mutations that alter substrate specificity.
Clinical and pathophysiological observations in migraine and tension-type headache explained by integration of vascular, supraspinal and myofascial inputs (1991)

A vascular-supraspinal-myogenic (VSM) model for pain in migraine based on our previous clinical and pathophysiological observations is proposed. According to the model, perceived pain (headache) intensity is determined by the sum of nociception from cephalic arteries and pericranial myofascial tissues converging upon the same neurons and integrated with supraspinal effects (usually facilitating). Vascular input predominates over myofascial input in migraine, whereas significance of supraspinal facilitation is difficult to estimate. The importance of these 3 effects may vary between patients and in the same individual with time. The model is in accordance with recent experimental studies showing convergence of somatovisceral afferents upon n. caudalis neurons. Also, long term potentiation due to nociceptive activation and sensitization of neurons to input from wider areas and non-nociceptive stimuli are relevant to our model. In tension-type headache, nociception is primarily myofascial, but vascular input cannot be disregarded. Supraspinal facilitation probably plays a large, sometimes dominant role (the MSV model). The model explains much of the complexity of the clinical picture of these disorders as well as their tendency to overlap and to change into one another. Also, a number of pathophysiological observations such as why muscles are tender during migraine, why trigger-point injection may cure migraine attacks and why chronic tension-type headache is often associated with episodes of pulsating pain, can be explained. The model gives a rational explanation of empirically developed, internationally accepted, multimodal treatment strategies for migraine and tension-type headache. It may thus serve a useful purpose in explaining the disorder to patients. Finally, the model points to several avenues of future research in animals and man.
A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism (2015)

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections and is the leading cause of infant hospitalizations. Recently, a promising vaccine antigen based on the RSV fusion protein (RSV F) stabilized in the native prefusion conformation has been described. Here we report alternative strategies to arrest RSV F in the prefusion conformation based on the prevention of hinge movements in the first refolding region and the elimination of proteolytic exposure of the fusion peptide. A limited number of unique mutations are identified that stabilize the prefusion conformation of RSV F and dramatically increase expression levels. This highly stable prefusion RSV F elicits neutralizing antibodies in cotton rats and induces complete protection against viral challenge. Moreover, the structural and biochemical analysis of the prefusion variants suggests a function for p27, the excised segment that precedes the fusion peptide in the polypeptide chain.
Removal of CO2by Calcium-Based Sorbents in the Presence of SO2 (2006)

In an investigation of in situ CO2 removal for fluidized-bed combustion processes, seven calcium-based sorbents were tested for simultaneous CO2 and SO2 removal using both an atmospheric thermogravimetric reactor and a pressurized thermogravimetric analyzer. SO2 was found to impede cyclic CO2 capture because of pore blockage by sulfate products, resulting primarily from direct sulfation during the later stage of each cycle. The sorbents showed similar patterns during cocapture. Loss in sorbent reversibility could not be prevented but was improved by higher CO2 partial pressures.
Chloroplastic Precursors and their Transport Across the Envelope Membranes (1989)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
Editing Soft Shadows in a Digital Photograph (2007)

This technique for modeling, editing, and rendering shadow edges in a photograph or a synthetic image lets users separate the shadow from the rest of the image and make arbitrary adjustments to its position, sharpness, and intensity.
Molecular Cloning of Human Endothelin (ET) Receptors ETA and ETB (1992)

Complementary DNAs coding for two different endothelin (ET) receptors were isolated from a human lung cDNA library. DNA sequencing revealed that they corresponded to either the ET-1-selective receptor subtype originally identified in cows (ETA) or the nonselective subtype first found in rats (ETB). An open reading frame coding for a 427 (ETA) or a 442 (ETB) amino acid-long protein, with a transmembrane topology also found in other G protein-coupled receptors, was determined. Whereas the amino acid identity is about 90% between the characterized members of a given receptor subtype, with the best conserved parts being the hydrophobic transmembrane domains, less than 60% identity was found between the human A and B subtypes. Southern blot analysis of human genomic DNA revealed the existence of multiple hybridizing bands when using probes derived from the full-length ETA or ETB cDNAs. However, when shorter fragments were selected as probes, only one band remained detectable, which suggests the existence of a single-copy gene for each subtype of ET receptor.
Time to abandon dogma: CD14 is expressed by non‐myeloid lineage cells (2005)

CD14 is a pattern recognition receptor; its important role in innate immunity is reviewed here. Since its discovery and subsequent classification at the first leucocyte typing workshop in 1982, CD14 has been thought of as a leucocyte differentiation antigen. However, it has become clear that CD14 is also expressed by many non-myeloid cells, and the evidence for this is presented. The possible role of the presence of low copy number CD14 on non-myeloid cells is discussed. It is time to acknowledge CD14 as an ubiquitous molecule and abandon the position that it is expressed by myeloid cells alone.
Review: Mediated Algorithms (2013)

Book Review| May 01 2013 Review: Mediated Algorithms Clive Holden: Media, Mediated Stephen Bulger GalleryToronto March 2–30, 2013 Matthew Ryan Smith Matthew Ryan Smith MATTHEW RYAN SMITH, PhD, is a writer, independent curator, and educator based in Toronto. His writings have been featured in several Canadian and international art publications including C Magazine, ArtUS, FUSE, Artinfo Canada, and Magenta. Search for other works by this author on: This Site PubMed Google Scholar Afterimage (2013) 40 (6): 20–21. https://doi.org/10.1525/aft.2013.40.6.20 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Matthew Ryan Smith; Review: Mediated Algorithms. Afterimage 1 May 2013; 40 (6): 20–21. doi: https://doi.org/10.1525/aft.2013.40.6.20 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAfterimage Search This content is only available via PDF. © 2013 Afterimage/Visual Studies Workshop, unless otherwise noted. Reprints require written permission and acknowledgment of previous publication in Afterimage.2013 Article PDF first page preview Close Modal You do not currently have access to this content.
Isolation of ovulatory-active substances from crops of Job's tears(Coix lacryma-jobi L. var. ma-yuen Stapf.). (1988)

Ovulatory-active substances were isolated from crops of Jpb's tears (Coix lacryma-jobi L. var. ma-yuen STAPF. Gramineae) with guidance by microscopic observation of oviducts of normal cycling female golden hamsters. These compounds were assigned as a 9 : 1 mixture of trans-feruloyl stigmastanol and trans-feruloyl campestanol (1), and a 9 : 1 mixture of their geometrical isomers (2) by chemical and spectral means. Synthesis of trans- and cis-feruloyl sigmastanol was also carried out. Substance 1 and the synthetic trans-feruloyl stigmastanol at 200 μg/d showed induction of ovulation and stimulation of ovarian follicular growth in female golden hamsters.
Overall Survival As the Outcome for Randomized Clinical Trials With Effective Subsequent Therapies (2011)

We review how overall survival (OS) comparisons should be interpreted with increasing availability of effective therapies that can be given subsequently to the treatment assigned in a randomized clinical trial (RCT). We examine in detail how effective subsequent therapies influence OS comparisons under varying conditions in RCTs. A subsequent therapy given after tumor progression (or relapse) in an RCT that works better in the standard arm than the experimental arm will lead to a smaller OS difference (possibly no difference) than one would see if the subsequent therapy was not available. Subsequent treatments that are equally effective in the treatment arms would not be expected to affect the absolute OS benefit of the experimental treatment but will make the relative improvement in OS smaller. In trials in which control arm patients cross over to the experimental treatment after their condition worsens, a smaller OS difference could be observed than one would see without cross-overs. In particular, use of cross-over designs in the first definitive evaluation of a new agent in a given disease compromises the ability to assess clinical benefit. In disease settings in which there is not an intermediate end point that directly measures clinical benefit, OS should be the primary end point of an RCT. The observed difference in OS should be considered the measure of clinical benefit to the patients, regardless of subsequent therapies, provided that the subsequent therapies used in both treatment arms follow the current standard of care.
Detection of 23 Immunogenic Pneumococcal Proteins Using Convalescent-Phase Serum (2000)

A genomic expression library of Streptococcus pneumoniae was screened with a convalescent-phase serum for immunoreactive proteins. Six known and 17 unknown pneumococcal proteins were detected. Five of the known proteins were surface-located virulence factors, and eight of the unknown proteins were putative membrane proteins.
Recent Developments of Transition-State Analogue Glycosidase Inhibitors of Non-Natural Product Origin (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRecent Developments of Transition-State Analogue Glycosidase Inhibitors of Non-Natural Product OriginVinni H. Lillelund, Henrik H. Jensen, Xifu Liang, and Mikael BolsView Author Information Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark Cite this: Chem. Rev. 2002, 102, 2, 515–554Publication Date (Web):January 29, 2002Publication History Received17 July 2001Published online29 January 2002Published inissue 1 February 2002https://pubs.acs.org/doi/10.1021/cr000433khttps://doi.org/10.1021/cr000433kresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views4416Altmetric-Citations630LEARN 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:Conformation,Inhibition,Inhibitors,Peptides and proteins,Transition states Get e-Alerts
Multimodal Learning with Deep Boltzmann Machines (2012)

A Deep Boltzmann Machine is described for learning a generative model of data that consists of multiple and diverse input modalities. The model can be used to extract a unified representation that fuses modalities together. We find that this representation is useful for classification and information retrieval tasks. The model works by learning a probability density over the space of multimodal inputs. It uses states of latent variables as representations of the input. The model can extract this representation even when some modalities are absent by sampling from the conditional distribution over them and filling them in. Our experimental results on bi-modal data consisting of images and text show that the Multimodal DBM can learn a good generative model of the joint space of image and text inputs that is useful for information retrieval from both unimodal and multimodal queries. We further demonstrate that this model significantly outperforms SVMs and LDA on discriminative tasks. Finally, we compare our model to other deep learning methods, including autoencoders and deep belief networks, and show that it achieves noticeable gains. 1
Poor Survival Associated with the BRAF V600E Mutation in Microsatellite-Stable Colon Cancers (2005)

The BRAF V600E mutation has been associated with microsatellite instability and the CpG island methylator phenotype (CIMP) in colon cancer. We evaluated a large population-based sample of individuals with colon cancer to determine its relationship to survival and other clinicopathologic variables. The V600E BRAF mutation was seen in 5% (40 of 803) of microsatellite-stable tumors and 51.8% (43 of 83) of microsatellite-unstable tumors. In microsatellite-stable tumors, this mutation was related to poor survival, CIMP high, advanced American Joint Committee on Cancer (AJCC) stage, and family history of colorectal cancer [odds ratio, 4.23; 95% confidence interval (95% CI), 1.65-10.84]. The poor survival was observed in a univariate analysis of 5-year survival (16.7% versus 60.0%; P < 0.01); in an analysis adjusted for age, stage, and tumor site [hazard rate ratio (HRR), 2.97; 95% CI, 2.05-4.32]; in stage-specific, age-adjusted analyses for AJCC stages 2 to 4 (HRR, 4.88, 3.60, and 2.04, respectively); and in Kaplan-Meier survival estimates for AJCC stages 2 to 4 (P < 0.01 for all three stages). Microsatellite-unstable tumors were associated with an excellent 5-year survival whether the V600E mutation was present or absent (76.2% and 75.0%, respectively). We conclude that the BRAF V600E mutation in microsatellite-stable colon cancer is associated with a significantly poorer survival in stages 2 to 4 colon cancer but has no effect on the excellent prognosis of microsatellite-unstable tumors.
Compiler Support for Reducing Leakage Energy Consumption (2003)

Current trends indicate that leakage energy consumption will be an important concern in upcoming process technologies. In this paper, we propose a compiler-based leakage energy optimization strategy. Our strategy is built upon a data-flow analysis that identifies basic blocks that do not use a given functional unit. Based on this information, the compiler then inserts activate/deactivate instructions in the code to set/reset a sleep signal which controls leakage current for functional units. Our experimental results show that the proposed compiler-based strategy is very effective in reducing leakage energy of functional units.
MagA is sufficient for producing magnetic nanoparticles in mammalian cells, making it an MRI reporter (2008)

Magnetic resonance imaging (MRI) is routinely used to obtain anatomical images that have greatly advanced biomedical research and clinical health care today, but the full potential of MRI in providing functional, physiological, and molecular information is only beginning to emerge. In this work, we sought to provide a gene expression marker for MRI based on bacterial magnetosomes, tiny magnets produced by naturally occurring magnetotactic bacteria. Specifically, magA, a gene in magnetotactic bacteria known to be involved with iron transport, is expressed in a commonly used human cell line, 293FT, resulting in the production of magnetic, iron-oxide nanoparticles by these cells and leading to increased transverse relaxivity. MRI shows that these particles can be formed in vivo utilizing endogenous iron and can be used to visualize cells positive for magA. These results demonstrate that magA alone is sufficient to produce magnetic nanoparticles and that it is an appropriate candidate for an MRI reporter gene.
Role of the Heat Shock Protein 90 in Immune Response Stimulation by Bacterial DNA and Synthetic Oligonucleotides (2001)

To elucidate the mechanisms of immunostimulation by bacterial DNA and synthetic oligonucleotides, the effects of heat shock protein 90 (Hsp90) inhibitors on the activation of murine spleen cells and macrophages by these molecules were investigated. Murine spleen cells and J774 and RAW264.7 macrophages responded to a CpG-containing oligodeoxynucleotide (CpG ODN) and Escherichia coli DNA by increased production of interleukin 6 (IL-6), IL-12, tumor necrosis factor alpha, and nitric oxide (NO). Pretreatment with any of the three Hsp90 inhibitors geldanamycin, radicicol, and herbimycin A resulted in a dose-dependent suppression of cytokine production from the spleen cells and macrophages and of NO from macrophages stimulated with CpG ODN or E. coli DNA. These Hsp90 inhibitors, however, had no effect on Staphylococcus aureus Cowan strain 1-induced IL-12 production from either the murine spleen cells or macrophages. CpG ODN and E. coli DNA induced increased intracellular levels of phosphorylated extracellular signal-regulated kinases (ERK1 and -2), which are members of the mitogen-activated protein (MAP) kinase family, while geldanamycin and radicicol blocked the phosphorylation of ERK1 and -2 in J774 and RAW264.7 cells. These data indicate that DNA-induced activation of murine spleen cells and macrophages is mediated by Hsp90 and that Hsp90 inhibitor suppression of DNA-induced macrophage activation is associated with disruption of the MAP kinase signaling pathway. Our findings suggest that Hsp90 inhibitors may provide a useful means of elucidating the mechanisms of immunostimulation by bacterial DNA and CpG ODN as well as a strategy for preventing adverse effects of bacterial DNA as well as lipopolysaccharide.
Baboon-to-human cardiac xenotransplantation in a neonate (1985)

This report details the first case of cardiac xenotransplantation in a neonate. The recipient, a victim of hypoplastic left heart syndrome (HLHS), survived 20 days. Autopsy findings are documented. The cardiac graft showed only traces of cell-mediated rejection. Graft failure appears to have resulted from a progressive, potentially avoidable humoral response, unmodified by immunosuppression. Cardiac allotransplantation and selective baboon-to-human xenotransplantation deserve further exploration as investigational therapy for neonatal HLHS.
Correlation of Natural Gases with Their Sources (1994)

The petroleum system concept is a reliable and logical way to judge and describe the petroleum potential and exploration risks of undrilled propects, plays, and basins. In 19 chapters on petroleum system basics and 18 case study chapters, this comprehensive volume provides an integrated look at the processes of petroleum generation in active source rocks, migration, and accumulation in traps.
DNA duplexes stabilized by modified monomer residues: synthesis and stability (1998)

The synthesis of a series of 2′-deoxyuridine analogues modified at the 5-position and a series of 2′-deoxypurines modified at the 8-position is described. Ultraviolet melting studies have been used to assess the stability of DNA duplexes 12- and 8-residues in length that contain these modifications. Of those modified residues which have been incorporated into oligonucleotides, 5-(prop-1-ynyl)-2′-deoxyuridine is found to impart the greatest increase in stability on the DNA duplexes studied.Thermodynamic analyses show that the reason for this increase in stability arises from a decrease in enthalpy which is related to the DNA base stacking process. We suggest that the degree of stabilisation imparted by the propyne moiety may be sequence dependent.