gebhart/patrepeval huggingface dataset:
Simultaneous Measurement of Ionic Current and Fluorescence from Single Protein Pores (2009)

The ability to simultaneously monitor both the ionic current and fluorescence from membrane channels and pores has the potential to link structural changes with function in such proteins. We present a new method for simultaneously measuring single-channel electrical currents and fluorescence from membrane proteins by using water-in-oil droplet bilayers. We demonstrate the simultaneous fluorescence and electrical detection of stochastic blocking by cyclodextrin in multiple staphylococcal alpha-hemolysin pores. The combined fluorescence signal from individual pores exhibits the same sequence of blocking events as the total current recording, showing that the two signals from each pore are correlated.
In Silico Binding Free Energy Predictability by Using the Linear Interaction Energy (LIE) Method:  Bromobenzimidazole CK2 Inhibitors as a Case Study (2007)

Protein kinase CK2 is essential for cell viability, and its control regards a broad series of cellular events such as gene expression, RNA, and protein synthesis. Evidence of its involvement in tumor development and viral replication indicates CK2 as a potential target of antineoplastic and antiviral drugs. In this study the Linear Interaction Energy (LIE) Method with the Surface Generalized Born (SGB) continuum solvation model was used to study several bromobenzimidazole CK2 inhibitors. This methodology, developed by Aqvist, finds a plausible compromise between accuracy and computational speed in evaluating binding free energy (DeltaGbind) values. In this study, two different free binding energy models, named "CK2scoreA" and "CK2scoreB", were developed using 22 inhibitors as the training set in a stepwise approach useful to appropriately select both the tautomeric form and the starting binding position of each inhibitor. Both models are statistically acceptable. Indeed, the better one is characterized by a correlation coefficient (r2) of 0.81, and the predictive accuracy was 0.65 kcal/mol. The corresponding validation, using an external test set of 16 analogs, showed a correlation coefficient (q2) of 0.68 and a prediction root-mean-square error of 0.78 kcal/mol. In this case, the LIE approach has been proved to be an efficient methodology to rationalize the difference of activity, the key interactions, and the different possible binding modes of this specific class of potent CK2 inhibitors.
Differential Temporal Expression of Members of the Transforming Growth Factor β Superfamily During Murine Fracture Healing (2002)

Fracture healing is a unique postnatal repair process in which the events of endochondral and intramembranous bone formation follow a definable temporal sequence. The temporal patterns of messenger RNA (mRNA) expression for members of the transforming growth factor beta (TGF-beta) superfamily were examined over a 28-day period of fracture healing in mouse tibias. Bone morphogenetic protein 2 (BMP-2) and growth and differentiation factor 8 (GDF8) showed maximal expression on day 1 after fracture, suggesting their roles as early response genes in the cascade of healing events. Restricted expression of GDF8 to day 1, in light of its known actions as a negative regulator of skeletal muscle growth, suggests that it may similarly regulate cell differentiation early in the fracture healing process. GDF5, TGF-beta2, and TGF-beta3 showed maximal expression on day 7, when type II collagen expression peaked during cartilage formation. In contrast, BMP-3, BMP-4, BMP-7, and BMP-8 showed a restricted period of expression from day 14 through day 21, when the resorption of calcified cartilage and osteoblastic recruitment were most active. TGF-beta1, BMP-5 and BMP-6, and GDF10 were constitutively expressed from day 3 to day 21. However, during the same time period, GDF3, GDF6, and GDF9 could not be detected, and GDF1 was expressed at extremely low levels. These findings suggest that several members of the TGF-beta superfamily are actively involved in fracture healing and although they are closely related both structurally and functionally, each has a distinct temporal expression pattern and potentially unique role in fracture healing.
Signaling Recognition Events with Fluorescent Sensors and Switches (1997)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSignaling Recognition Events with Fluorescent Sensors and SwitchesA. Prasanna de Silva, H. Q. Nimal Gunaratne, Thorfinnur Gunnlaugsson, Allen J. M. Huxley, Colin P. McCoy, Jude T. Rademacher, and Terence E. RiceView Author Information School of Chemistry, Queen's University, Belfast BT9 5AG, Northern Ireland Cite this: Chem. Rev. 1997, 97, 5, 1515–1566Publication Date (Web):August 5, 1997Publication History Received6 December 1996Revised12 March 1997Published online5 August 1997Published inissue 1 August 1997https://pubs.acs.org/doi/10.1021/cr960386phttps://doi.org/10.1021/cr960386presearch-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views36299Altmetric-Citations6309LEARN 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:Cell signaling,Excited states,Fluorescence,Fluorophores,Receptors Get e-Alerts
Structure and distribution of alpha-1-microglobulin proteins (1998)

This thesis describes studies of the structure and tissue distribution of alpha-1-microglobulin (a1-m), a member of the lipocalin protein superfamily with immunosuppressive properies. It was shown that a1-m appears in human plasma in five major forms. These were identified as monomeric a1-m and covalent complexes between a1-m and IgA, prothrombin, albumin and a1-m. In addition to blood, both monomeric-, and high molecular weight forms of a1-m were present in tissues. The liver, kidney and heart contained a series of a1-m isoforms with apparent molecular masses between 40 kDa and 50 kDa, which were not present in plasma. Immunohistochemical analysis of human tissue demonstrated intracellular labeling of a1-m in hepatocytes and in the proximal epithelial cells of the kidney. In addition, a1-m immunoreactivity was detected in the interstitial connective tissue of heart, lung and in the adventitia of blood vessels as well as on cell surfaces of cardiocytes. a1-m mRNA was detected only in the liver and pancreas. This suggests that the protein found in other tissues is not synthesized locally, but transported to the tissues via the bloodstream from the production sites in liver and pancreas. a1-m was found in placenta particularly at sites of syncytiotrophoblast injury. Thus, ?tissue a1-m? may act as a local immunosuppressive barrier in the placenta, protecting the chorionic villi from the immune system of the mother. a1-m is yellow-brown. Colored tryptic peptides of a1-m were purified, and it was shown that the side chains of Lys92, Lys118 and Lys130 in these peptides carried size heterogeneous covalently attached groups with molecular masses beetween 106 and 282 Da. The fluorescence properties and molecular modeling suggested that the chromophores were most likely buried and closely spaced in the interior of the protein. Only the free a1m carried colored groups, whereas the a1m linked to IgA was uncolored.
Microbial complexes in subgingival plaque (1998)

It has been recognized for some time that bacterial species exist in complexes in subgingival plaque. The purpose of the present investigation was to attempt to define such communities using data from large numbers of plaque samples and different clustering and ordination techniques. Subgingival plaque samples were taken from the mesial aspect of each tooth in 185 subjects (mean age 51 +/- 16 years) with (n = 160) or without (n = 25) periodontitis. The presence and levels of 40 subgingival taxa were determined in 13,261 plaque samples using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments were made at 6 sites per tooth at each visit. Similarities between pairs of species were computed using phi coefficients and species clustered using an averaged unweighted linkage sort. Community ordination was performed using principal components analysis and correspondence analysis. 5 major complexes were consistently observed using any of the analytical methods. One complex consisted of the tightly related group: Bacteroides forsythus, Porphyromonas gingivalis and Treponema denticola. The 2nd complex consisted of a tightly related core group including members of the Fusobacterium nucleatum/periodonticum subspecies, Prevotella intermedia, Prevotella nigrescens and Peptostreptococcus micros. Species associated with this group included: Eubacterium nodatum, Campylobacter rectus, Campylobacter showae, Streptococcus constellatus and Campylobacter gracilis. The 3rd complex consisted of Streptococcus sanguis, S. oralis, S. mitis, S. gordonii and S. intermedius. The 4th complex was comprised of 3 Capnocytophaga species, Campylobacter concisus, Eikenella corrodens and Actinobacillus actinomycetemcomitans serotype a. The 5th complex consisted of Veillonella parvula and Actinomyces odontolyticus. A. actinomycetemcomitans serotype b, Selenomonas noxia and Actinomyces naeslundii genospecies 2 (A. viscosus) were outliers with little relation to each other and the 5 major complexes. The 1st complex related strikingly to clinical measures of periodontal disease particularly pocket depth and bleeding on probing.
Evaluating knowledge transfer and zero-shot learning in a large-scale setting (2011)

While knowledge transfer (KT) between object classes has been accepted as a promising route towards scalable recognition, most experimental KT studies are surprisingly limited in the number of object classes considered. To support claims of KT w.r.t. scalability we thus advocate to evaluate KT in a large-scale setting. To this end, we provide an extensive evaluation of three popular approaches to KT on a recently proposed large-scale data set, the ImageNet Large Scale Visual Recognition Competition 2010 data set. In a first setting they are directly compared to one-vs-all classification often neglected in KT papers and in a second setting we evaluate their ability to enable zero-shot learning. While none of the KT methods can improve over one-vs-all classification they prove valuable for zero-shot learning, especially hierarchical and direct similarity based KT. We also propose and describe several extensions of the evaluated approaches that are necessary for this large-scale study.
T Cell-Dependent B Cell Activation (1993)

B cells obtain help from T cells in the antibody response by acting as antigen-specific antigen presenting cells. A direct signal through binding of antigen to membrane Ig can enhance B cell antigen presentation and T-dependent B cell activation, but is not required for a productive interaction between a small resting B cell and a differentiated helper T cell. As a result of helper T cell recognition of antigen on the B cell surface, the T cell becomes activated and in turn activates the B cell. T cell help has two components: lymphokines which act as growth and differentiation factors for B cells, and additional signals which require cell contact and enable B cells to respond to lymphokines. Contact help activity is regulated like lymphokine synthesis and secretion. Because contact help activity is retained by fixed, activated helper T cells and plasma membranes prepared from activated T cells, contact help is likely to be owing to new proteins expressed as membrane-bound lymphokines or activation antigens on helper T cells. Once induced, contact help can be delivered to B cells independently of recognition of antigen/class II MHC. A newly identified activation antigen of helper T cells, a ligand for the B cell differentiation antigen, CD40, is a key component of contact help. The roles of other T and B cell membrane molecules in contact help are reviewed.
A Bayesian Evolutionary Distance for Parametrically Aligned Sequences (1996)

There is an inherent relationship between the process of pairwise sequence alignment and the estimation of evolutionary distance. This relationship is explored and made explicit. Assuming an evolutionary model and given a specific pattern of observed base mismatches, the relative probabilities of evolution at each evolutionary distance are computed using a Bayesian framework. The mean or the median of this probability distribution provides a robust estimate of the central value. The evolutionary distance has traditionally been computed as zero for an observed homology of 20 bases with no mismatches; we prove that it is highly probable that the distance is greater than 0.01. The mean of the distribution is 0.047, which is a better estimate of the evolutionary distance. Bayesian estimates of the evolutionary distance incorporate arbitrary prior information about variable mutation rates both over time and along sequence position, thus requiring only a weak form of the molecular-clock hypothesis. The endpoints of the similarity between genomic DNA sequences are often ambiguous. The probability of evolution at each evolutionary distance can be estimated over the entire set of alignments by choosing the best alignment at each distance and the corresponding probability of duplication at that evolutionary distance. A central value of this distribution provides a robust evolutionary distance estimate. We provide an efficient algorithm for computing the parametric alignment, considering evolutionary distance as the only parameter. These techniques and estimates are used to infer the duplication history of the genomic sequence in C. elegans and in S. cerevisiae. Our results indicate that repeats discovered using a single scoring matrix show a considerable bias in subsequent evolutionary distance estimates.
Species Differences in Prostatic Steroid 5α-Reductases of Rat, Dog, and Human (1985)

The conversion of testosterone to 5 alpha-dihydrotestosterone by prostate particulates from rats, dogs, and humans was investigated, and significant species differences were found with their pH profiles, affinities for 4-azasteroidal inhibitors, and sensitivities to mercuric sulfhydryl reagents. The pH optima for the rat (pH 7), the dog (pH 6), and the human (pH 5) enzyme are significantly different. Mersalyl acid and p-hydroxymercuribenzoate inactivate only the rat 5 alpha-reductase, but not the human or dog enzyme. The rank orders of potencies of 24 3-oxo-4-azasteroids to inhibit 5 alpha-reductases of the rat, dog, and human prostate are different. The variation of the 17 beta-functional groups of the inhibitors demonstrates clearly the species differences. Those inhibitors with a 17 beta-diethylcarbamoyl, 17 beta-diisopropylcarbamoyl, 17 beta-t-butylcarbamoyl, or 17 beta-secbutylcarbonyl functional group are approximately equipotent as inhibitors of the rat and human enzymes, whereas they are only 0.1-15% as potent as inhibitors of the dog enzyme. On the other hand, those inhibitors with a 17 beta-spiroether functional group are most potent as inhibitors of the rat enzyme, are 15-50% as potent as inhibitors of the dog enzyme, and are 0.2-0.4% as potent as inhibitors of the human enzyme. Those inhibitors with a 17 beta-n-octylcarbamoyl, 17 beta-(1-carboxyethyl), or 17 beta-(1-carboxy-3-butyl) functional group are 2-3 orders of magnitude less potent as inhibitors of the dog and human enzymes than as inhibitors of the rat enzyme. These results suggest that prostatic 5 alpha-reductases of rats, dogs, and humans are significantly different. In spite of the significant species differences in inhibitor affinities, where determined, inhibition of the rat, dog and human enzymes by these compounds is competitive with testosterone. These 3-oxo-4-azasteroids have a similar rank order of potency as inhibitors of 5 alpha-reductase in human normal, benign hyperplastic, and cancerous prostates, indicating that the inhibitor-binding sites of 5 alpha-reductase in the prostate in different pathological states are similar. The affinities of the 3-oxo-4-azasteroids for rat prostatic cytosol receptor were determined. Five of these 5 alpha-reductase inhibitors have no significant affinity for the androgen receptor, whereas others do have an affinity for the receptor.
Manuscript Indications of Change of Speaker in Aristophanes' Acharnians (2001)

Aristophanes' Acharnians is preserved in five papyri dating from the 2nd to the 6th c. C.E. and in sixteen manuscripts, the oldest of which is the 10th century Ravennas 429 (R).1 Five of the sixteen manuscripts (Vbl = Barberinianus I, 45; E2 = Estensis III D 14; M9 = Ambrosianus L 41 sup.; Rml = Vallicellianus F 16; and A = Laurentianus 31, 16) were eliminated by Earnest Cary as copies of T, E, E, the Aldine, and B, respectively, and require no further consideration.2 As I argue in detail in my forthcoming edition of the play, the relationship among the remaining nine manuscripts and Marcus Musurus' 1498 Aldine edition is most economically represented in the following fashion:
Wilms' Tumor 1 Gene Expression in Hepatocellular Carcinoma Promotes Cell Dedifferentiation and Resistance to Chemotherapy (2009)

The Wilms' tumor 1 gene (WT1) encodes a transcription factor involved in cell growth and development. As we previously reported, WT1 expression is hardly detectable in normal hepatic tissue but is induced in liver cirrhosis. Although WT1 has been found to be overexpressed in a number of malignancies, the role of WT1 in hepatocarcinogenesis has not been clarified. We found that WT1 is expressed in several human hepatocellular carcinoma (HCC) cell lines, including PLC/PRF/5 and HepG2, and in HCC tumor tissue in 42% of patients. WT1 small interfering RNAs did not affect proliferation rate of HCC cells but abrogated their resistance to anoikis. Transcriptome analysis of PLC/PRF/5 cells after WT1 knockdown showed up-regulation of 251 genes and down-regulation of 321. Ninety percent of the former corresponded to metabolic genes, mostly those characterizing the mature hepatocyte phenotype. On the contrary, genes that decreased upon WT1 inhibition were mainly related to defense against apoptosis, cell cycle, and tumor progression. In agreement with these findings, WT1 expression increased the resistance of liver tumor cells to doxorubicin, a compound used to treat HCC. Interestingly, doxorubicin strongly enhanced WT1 expression in both HCC cells and normal human hepatocytes. Among different chemotherapeutics, induction of WT1 transcription was restricted to topoisomerase 2 inhibitors. When WT1 expression was prohibited, doxorubicin caused a marked increase in caspase-3 activation. In conclusion, WT1 is expressed in a substantial proportion of HCC contributing to tumor progression and resistance to chemotherapy, suggesting that WT1 may be an important target for HCC treatment.
Surface-enhanced Raman scattering for cancer diagnostics: detection of the BCL2 gene (2003)

A method of detection for cancer genes, such as B-cell lymphoma 2 gene, has been developed using surface-enhanced Raman scattering-active substrates. This method uses Raman active dye-labeled DNA gene probes and metallic nanostructures as surface-enhanced Raman scattering-active platforms. A self-assembled monolayer system composed of mercapto hexane-labeled, single-strand DNA (SH-(CH2)6-ssDNA/ 6-mercapto-1-hexanol) is formed on a silver surface. The Raman-active dye-labeled gene is hybridized with its complementary probe, which is immobilized on the silver surface. The surface-enhanced Raman gene probes in this study can be used to detect DNA targets via hybridization to complementary DNA probes. The probes do not involve the use of radioactive labels and have great potential to provide both sensitivity and selectivity. The utility of this approach is investigated.
Increased concentrations of omega-3 fatty acids in milk and platelet rich plasma of grass-fed cows. (1993)

Epidemiological data indicate that omega-3 fatty acids protect from cardiovascular diseases and hyperlipidemia. Cold water fish is the major recognized source of omega-3 fatty acids but fish is not a staple food in many countries. Since terrestrial green plants may also represent a source of omega-3 fatty acids we tested the hypothesis that platelet rich plasma and milk from cows feeding exclusively on green grass contains more omega-3 fatty acids than milk from cows fed conserved grass. The relative concentrations of linolenic acid (18:3) and eicosapentaenoic acid (20:5) and the ratio of eicosapentaenoic acid to arachidonic acid (20:4) which is critical for the formation of omega-3 derived eicosanoids were significantly higher in milk from grass fed cows. Similar changes were seen in the fatty acid composition of platelets. Half a liter of milk from grass-fed cows provides approximately 191 mg 18:3 and 14 mg 20:5. In this regard milk from grass fed cows may be nutritionally superior to milk from cows eating conserved grass.
Population Dynamics of a Naturally Occurring Heterogeneous Mixture ofBorrelia burgdorferiClones (1999)

Two unique isolates of Borrelia burgdorferi, differing in plasmid content and outer surface protein C expression, were cultured on sequential captures of a single free-living Peromyscus leucopus mouse and were examined for differences in transmissibility. Both isolates were transmissible from inoculated C.B-17 mice to larval Ixodes scapularis ticks and, subsequently, from infected nymphal ticks to C3H/HeJ mice. Plasmid and protein analyses suggested that the original isolates were a mixed population of B. burgdorferi, and cloning by limiting dilution resulted in the identification of two clonal groups. In addition to being heterogeneous in plasmid and genomic macrorestriction analyses, the clones varied with respect to the electrophoretic mobilities and antigenicity of their OspC proteins, as shown by their reactivity to a panel of monoclonal antibodies. Plasmid analysis of sequential isolates from C3H mice experimentally infected with the primary isolate or various mixtures of its subclones showed an apparently random fluctuation in clonal dominance in the majority of mice. Surprisingly, mice infected with each subclone were permissive to superinfection with the heterologous subclone, despite the presence of anti-B. burgdorferi antibodies at the time of the secondary challenge. These results show conclusively that mice captured at Lyme disease enzootic sites may be infected by mixed populations of genetically and antigenically distinct B. burgdorferi clones and that these infections can be acquired by coinfection or by sequential infection. The lack of cross-immunization between clones existing within a naturally occurring population may play a role in the maintenance of the genetic heterogeneity of B. burgdorferi in nature.