gebhart/patrepeval huggingface dataset:
Macrophage Apoptosis by Anthrax Lethal Factor Through p38 MAP Kinase Inhibition (2002)

The bacterium Bacillus anthracis causes the death of macrophages, which may allow it to avoid detection by the innate immune system. We found that B. anthracis lethal factor (LF) selectively induces apoptosis of activated macrophages by cleaving the amino-terminal extension of mitogen-activated protein kinase (MAPK) kinases (MKKs) that activate p38 MAPKs. Because macrophages that are deficient in transcription factor nuclear factor kappaB (NF-kappaB) are also sensitive to activation-induced death and p38 is required for expression of certain NF-kappaB target genes, p38 is probably essential for synergistic induction of those NF-kappaB target genes that prevent apoptosis of activated macrophages. This dismantling of the p38 MAPK module represents a strategy used by B. anthracis to paralyze host innate immunity.
Site-Directed Mutagenesis and Expression of the Soluble Form of the Family IIIa Cellulose Binding Domain from the Cellulosomal Scaffolding Protein of Clostridium cellulovorans (2005)

The planar and anchoring residues of the family IIIa cellulose binding domain (CBD) from the cellulosomal scaffolding protein of Clostridium cellulovorans were investigated by site-directed mutagenesis and cellulose binding studies. By fusion with maltose binding protein, the family IIIa recombinant wild-type and mutant CBDs from C. cellulovorans were expressed as soluble forms. Cellulose binding tests of the mutant CBDs indicated that the planar strip residues played a major role in cellulose binding and that the anchoring residues played only a minor role.
Optical properties of biological tissues: a review (2013)

A review of reported tissue optical properties summarizes the wavelength-dependent behavior of scattering and absorption. Formulae are presented for generating the optical properties of a generic tissue with variable amounts of absorbing chromophores (blood, water, melanin, fat, yellow pigments) and a variable balance between small-scale scatterers and large-scale scatterers in the ultrastructures of cells and tissues.
Expression of dominant negative CREB reduces resistance to radiation of human melanoma cells. (1996)

u.v.-responsive element (URE)-binding proteins were found to include members of the AP1 and ATF transcription factor families. To elucidate the functional contribution of URE-bound proteins to the characteristics of human melanoma, we have used a dominant negative CREB cDNA which is mutated within the DNA-binding domain and cloned into a mammalian expression vector driven by the RSV promoter (KCREB). As such, KCREB is still capable of heterodimerizing with its associated proteins, yet, due to its poor binding affinity to DNA it out competes transcriptional activity mediated by those proteins. Human melanoma cells (MeWo) were transfected with KCREB and three clones, designated K1, K2, and K10 which express KCREB transcripts were then selected for further characterization. When tested for binding activities in gel shift assays, proteins prepared from the three clones exhibited a different set of complexes than the parent MeWo and control MeWo(neo) cells (transfected with empty expression vector) under normal growth conditions, and after u.v.-irradiation. Using CAT vector, driven by a tetramer URE construct, revealed a striking decrease in transcriptional activity in each of the three clones before as well as after u.v.-irradiation. When tested for radiation resistance MeWo cells were found to exhibit 42% survival to a u.v.-dose of 16 J/m2, whereas, K1, K2 and K10 exhibited only 10.2, 3.9 and 4.2% survival, respectively. Exposure to 2 Gy of X-radiation led to 62.1% survival of MeWo as compared with 18.5% of K1 and 7.7% and 6.5% of K2 and K10, respectively. While no significant differences were noticed in their growth rate, all three clones exhibited fewer, and smaller colonies in soft agar, when compared with parent cells. These findings indicate that through their transcriptional activities, CREB and its associated proteins play an important role in the acquisition of characteristic phenotypes of human melanoma cells including resistance to u.v.-irradiation.
B7.1 Is a Quantitatively Stronger Costimulus Than B7.2 in the Activation of Naive CD8+ TCR-Transgenic T Cells (1998)

Using a TCR transgenic mouse bred onto a recombinase-activating gene-2-deficient background, we have examined the influence of B7.1 and B7.2 on activation of naive, CD8+ T cells in vitro. We found that B7.1 was a more potent costimulus than B7.2 for induction of proliferation and IL-2 production by naive CD8+ T cells. This difference appeared to be quantitative in nature, as determined using transfectants expressing various defined levels of B7.1 or B7.2, or using purified B7.1 or B7.2 fusion proteins. In contrast to the quantitative differences seen in stimulation of naive T cells, B7.1 and B7.2 were comparable in their ability to costimulate responses in T cells previously primed in vitro. In addition, primed, but not naive, T cells were capable of proliferating and producing IL-2 in response to a TCR stimulus alone, apparently in the absence of B7 costimulation. Lastly, we found that B7.1 and B7.2 were equivalently capable of driving differentiation of naive CD8+ T cells into an IL-4-producing phenotype when exogenous IL-4 was added to the primary culture or to an IFN-gamma-producing phenotype in the presence of IL-12. These results indicate that signals generated by B7.1 and B7.2 are qualitatively similar, but that B7.1 is quantitatively stronger than B7.2. Further, our results indicate that the activation state of the responding T cell may influence the efficiency with which the T cell can respond to a costimulatory signal provided by either B7.1 or B7.2.
Positional cloning of ZNF 217 and NABC 1 : Genes amplified at 20q13.2 and overexpressed in breast carcinoma (1998)

We report here the molecular cloning of an approximately 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of amplification. Analysis of the 1-Mb region produced evidence for five genes, ZNF217, ZNF218, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cyclophillin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidate oncogenes and were characterized in detail. NABC1 is predicted to encode a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lines in which it was amplified. ZNF217 is centrally located in the 260-kb common region of amplification, transcribed in multiple normal tissues, and overexpressed in all cell lines and tumors in which it is amplified and in two in which it is not. ZNF217 is predicted to encode alternately spliced, Kruppel-like transcription factors of 1,062 and 1,108 aa, each having a DNA-binding domain (eight C2H2 zinc fingers) and a proline-rich transcription activation domain.
A Statistical Model for Identifying Proteins by Tandem Mass Spectrometry (2003)

A statistical model is presented for computing probabilities that proteins are present in a sample on the basis of peptides assigned to tandem mass (MS/MS) spectra acquired from a proteolytic digest of the sample. Peptides that correspond to more than a single protein in the sequence database are apportioned among all corresponding proteins, and a minimal protein list sufficient to account for the observed peptide assignments is derived using the expectation-maximization algorithm. Using peptide assignments to spectra generated from a sample of 18 purified proteins, as well as complex H. influenzae and Halobacterium samples, the model is shown to produce probabilities that are accurate and have high power to discriminate correct from incorrect protein identifications. This method allows filtering of large-scale proteomics data sets with predictable sensitivity and false positive identification error rates. Fast, consistent, and transparent, it provides a standard for publishing large-scale protein identification data sets in the literature and for comparing the results obtained from different experiments.
Electron‐Deficient Alkynes as Cleavable Reagents for the Modification of Cysteine‐Containing Peptides in Aqueous Medium (2009)

An efficient method has been developed for the chemoselective cysteine modification of unprotected peptides and proteins in aqueous media through the formation of a vinyl sulfide linkage by using electron-deficient alkynes, including alkynoic amides, esters and alkynones. The terminal alkynone-modified peptides could be converted back into the unmodified peptides (81% isolated yield) by adding thiols under mild conditions. The usefulness of this thiol-assisted cleavage of the vinyl sulfide linkage in peptides has been exemplified by the enrichment of a cysteine-containing peptide (71% recovery) from a mixture of cysteine-containing and non-cysteine-containing peptides.
Creating a digital-vehicle proving ground (2003)

This installment presents the state of the art of ITS research in China, particularly the facilities and the proving ground for testing automated vehicles. To combine their strengths, in 2002 the ITSC, the Chinese Academy of Sciences, and the University of Arizona agreed to conduct joint research on a digital automobile proving ground (DAPG) for automated-vehicle driving tests based on their Beijing and Tucson facilities. The paper describes this international collaboration's status and progress.
Synthesis of 3‐phenyl‐2H‐1,4‐benzoxazin‐2‐one. Revision of some structural assignments (1977)

Abstract The reported synthesis of 3‐phcnyl‐2 H ‐1,4‐benzoxazin‐2‐one (II) via brominution of o ‐acel‐amidophenyl phcnaeyl ether (Scheme) leads in lael to the 7‐bromo‐3‐phenyl‐2 H ‐1,4‐benzoxazin‐2‐ol (VIII). The structure of the other synthetic intermediates is also revised and a one‐step synthesis of the lactone II is reported hy condensation of methyl phenylglyoxalale and o ‐amino‐phenol.
Spectral Properties of Topical Retinoids Prevent DNA Damage and Apoptosis After Acute UV‐B Exposure in Hairless Mice¶ (2005)

We showed in a recent study that topical retinyl palmitate prevented UV-B-induced DNA damage and erythema in humans. Given that retinyl palmitate is a precursor of retinoic acid, the biological form of vitamin A that acts through nuclear receptors, we wondered whether these protective effects toward UV-B exposure were either receptor dependent or linked to other properties of the retinoid molecule such as its spectral properties. We determined the epidermal retinoid profile induced by topical retinoic acid in hairless mice and analyzed its effect on markers of DNA photodamage (thymine dimers) and apoptosis following acute UV-B exposure; we compared these effects to those induced by other natural topical retinoids (retinaldehyde, retinol and retinyl palmitate) which do not directly activate the retinoid receptors. We then analyzed the direct action of these retinoids on UV-B-induced DNA damage and apoptosis in cultured A431 keratinocytes. Topical retinoic acid significantly decreased (approximately 50%) the number of apoptotic cells, as well as the formation of thymine dimers in the epidermis of mice exposed to acute UV-B. Interestingly, the other topical retinoids decreased apoptosis and DNA damage in a similar way. On the other hand, neither retinoic acid nor the other retinoids interfered with the apoptotic process in A431 keratinocytes exposed to UV-B, whereas DNA photodamage was slightly decreased. We conclude that the decrease of apoptotic cells in hairless mouse epidermis following topical retinoids and UV-B irradiation reflects a protection of the primary targets of UV-B (DNA) by a mechanism independent of the activation of retinoid nuclear receptors, rather than a direct inhibition of apoptosis.
Motility as an Intestinal Colonization Factor for Campylobacter jejuni (1985)

The colonization of the intestinal tract of suckling mice by Campylobacter jejuni was examined by orally challenging the mice with a wild-type strain and several nonmotile mutant strains which were isolated after treating the wild-type strain with mutagens. The wild-type strain had colonized the lower portion of the small intestine, the caecum and the colon 2 d after inoculation. Two nonmotile strains, one of which (M8) had lost all the flagellar structure including the filament, the hook and the basal structure, and the other (M1) which had lost only the filament region, were both cleared from the intestinal tract 2 d after challenge. Another nonmotile strain (M14), which had a complete flagellar structure like that of the wild-type strain, did not colonize and was cleared from the intestinal tract like the other nonmotile and nonflagellated strains. One atypically motile strain (M5), which had a shorter flagellar filament than that of the wild-type strain, colonized the intestinal tract only when mice were challenged with a large inoculum. None of the mice challenged with either the wild-type or any of the mutant strains showed signs of illness. We concluded that motility is an important factor in the colonization of the intestinal tract of suckling mice by C. jejuni.
Using a suite of ontologies for preserving workflow-centric research objects (2015)

Scientific workflows are a popular mechanism for specifying and automating data-driven in silico experiments. A significant aspect of their value lies in their potential to be reused. Once shared, workflows become useful building blocks that can be combined or modified for developing new experiments. However, previous studies have shown that storing workflow specifications alone is not sufficient to ensure that they can be successfully reused, without being able to understand what the workflows aim to achieve or to re-enact them. To gain an understanding of the workflow, and how it may be used and repurposed for their needs, scientists require access to additional resources such as annotations describing the workflow, datasets used and produced by the workflow, and provenance traces recording workflow executions. In this article, we present a novel approach to the preservation of scientific workflows through the application of research objects—aggregations of data and metadata that enrich the workflow specifications. Our approach is realised as a suite of ontologies that support the creation of workflow-centric research objects. Their design was guided by requirements elicited from previous empirical analyses of workflow decay and repair. The ontologies developed make use of and extend existing well known ontologies, namely the Object Reuse and Exchange (ORE) vocabulary, the Annotation Ontology (AO) and the W3C PROV ontology (PROVO). We illustrate the application of the ontologies for building Workflow Research Objects with a case-study that investigates Huntington’s disease, performed in collaboration with a team from the Leiden University Medial Centre (HG-LUMC). Finally we present a number of tools developed for creating and managing workflow-centric research objects.
Plugfest 2009: Global interoperability in Telerobotics and telemedicine (2010)

Despite the great diversity of teleoperator designs and applications, their underlying control systems have many similarities. These similarities can be exploited to enable inter-operability between heterogeneous systems. We have developed a network data specification, the Interoperable Telerobotics Protocol, that can be used for Internet based control of a wide range of teleoperators. In this work we test interoperable telerobotics on the global Internet, focusing on the telesurgery application domain. Fourteen globally dispersed telerobotic master and slave systems were connected in thirty trials in one twenty four hour period. Users performed common manipulation tasks to demonstrate effective master-slave operation. With twenty eight (93%) successful, unique connections the results show a high potential for standardizing telerobotic operation. Furthermore, new paradigms for telesurgical operation and training are presented, including a networked surgery trainer and upper-limb exoskeleton control of micro-manipulators.
Hypoadiponectinemia Is Associated with Insulin Resistance, Hypertriglyceridemia, and Fat Redistribution in Human Immunodeficiency Virus-Infected Patients Treated with Highly Active Antiretroviral Therapy (2003)

A lipodystrophic syndrome and metabolic abnormalities have been observed in HIV-infected patients treated with highly active antiretroviral therapy (HAART). A murine model of lipodystrophy is associated with decreased levels of adiponectin, an adipocyte-secreted protein, the administration of which improves the metabolic syndrome in these mice. To investigate the association of adiponectin with metabolic changes in human lipodystrophy, we conducted a cross-sectional study of 112 HIV-infected patients treated with HAART. Mean adiponectin levels were higher in patients with no fat redistribution (FR) vs. FR (4.8 +/- 5.0 vs. 2.2 +/- 2.7 microg/ml, P < 0.01), but no significant differences in adiponectin levels were observed between FR subgroups. The difference in adiponectin levels between subjects with and without FR remained significant after adjusting for age, gender, leptin, HIV medication use, and CD4 count using logistic regression (odds ratio, 0.54, P = 0.008). Adiponectin was significantly correlated with triglycerides (r = -0.40), abdominal visceral fat (r = -0.35), extremity fat (r = 0.37), insulin resistance (HOMA-IR) (r = -0.28), nucleoside reverse transcriptase inhibitor (NRTI) use (r = -0.32), and high-density lipoprotein (HDL) (r = 0.41) using bivariate analysis (all P < 0.01). The association with HDL weakened but remained significant on multivariate analysis (standard beta = 0.29, P = 0.01). However, the association of adiponectin with HOMA-IR became nonsignificant after adjusting for NRTI use (standard beta = -0.15, P = 0.12), suggesting that changes in adiponectin levels may underlie the effect of NRTI use on insulin resistance. The associations of adiponectin with triglycerides and HOMA-IR were also slightly weakened after adjusting for visceral and extremity fat, indicating that adiponectin may, in part, mediate the effect of FR on triglycerides and insulin resistance. This study indicates that adiponectin is inversely correlated with abdominal visceral fat mass, serum triglycerides, and insulin resistance and is directly correlated with HDL and extremity fat in a sample of HIV-infected patients treated with HAART. The results also indicate that NRTI use may worsen insulin resistance by decreasing adiponectin levels. Thus, adiponectin replacement may be a potential treatment option to ameliorate the metabolic changes observed in this patient population.
Clinical evaluation of automated refraction in anterior chamber pseudophakia. (1991)

Automated refraction with the Canon RK-1 Autoref keratometer was evaluated in 85 eyes of 85 patients with an anterior chamber intraocular lens implant and a best corrected visual acuity of at least 6/12. Autorefraction readings were obtained in 80 (94%) of these eyes. The agreement between autorefraction and clinical refraction data was 89% for spherical equivalence less than 0.51 dioptres (D), 91% for sphere power less than 0.51 D, 82% for cylinder power less than 0.51 D, and 91% for cylinder axis less than 11 degrees. Autorefraction provides acceptably accurate postoperative refraction values in anterior chamber pseudophakia.
In vivo antitumor effect of the mTOR inhibitor CCI‐779 and gemcitabine in xenograft models of human pancreatic cancer (2005)

Mammalian target of rapamycin (mTOR) is considered to be a major effector of cell growth and proliferation that controls protein synthesis through a large number of downstream targets. We investigated the expression of the phosphatidylinositol 3'-kinase (PI3K)/mTOR signaling pathway in human pancreatic cancer cells and tissues, and the in vivo antitumor effects of the mTOR inhibitor CCI-779 with/without gemcitabine in xenograft models of human pancreatic cancer. We found that the Akt, mTOR and p70 S6 kinase (S6K1) from the PI3K/mTOR signaling pathway were activated in all of the pancreatic cancer cell lines examined. When surgically resected tissue specimens of pancreatic ductal adenocarcinoma were examined, phosphorylation of Akt, mTOR and S6K1 was detected in 50, 55 and 65% of the specimens, respectively. Although CCI-779 had no additive or synergistic antiproliferative effect when combined with gemcitabine in vitro, it showed significant antitumor activity in the AsPC-1 subcutaneous xenograft model as both a single agent and in combination with gemictabine. Furthermore, in the Suit-2 peritoneal dissemination xenograft model, the combination of these 2 drugs achieved significantly better survival when compared with CCI-779 or gemcitabine alone. These results demonstrate promising activity of the mTOR inhibitor CCI-779 against human pancreatic cancer, and suggest that the inhibition of mTOR signaling can be exploited as a potentially tumor-selective therapeutic strategy.
Single-channel recordings from purified acetylcholine receptors reconstituted in bilayers formed at the tip of patch pipets (1983)

The channel of the purified acetylcholine receptor from Torpedo californica electric organ reconstituted in lipid vesicles was assayed by direct electrical recording using patch-clamp pipets. High-resistance seals were obtained by gentle suction of vesicles into the pipet or after the formation of lipid bilayers from monolayers at the tip of the pipet. Single-channel currents were activated by three cholinergic ligands: acetylcholine, carbamylcholine, and suberyldicholine. The single-channel conductance, gamma, was 40 +/- 5 pS in 0.5 M NaCl, irrespective of the agonist used. The distributions of channel open times were fitted by a sum of two exponentials. The lifetimes of the two exponential components were a factor of 2 longer for suberyldicholine than for acetylcholine or carbamylcholine. At desensitizing concentrations of agonists the single events appeared in paroxysms of channel activity followed by quiescent periods. These results suggest that the full cycle of solubilization, purification, and reconstitution of this membrane receptor can be achieved without impairment of channel function.
Methods of Information Geometry (2007)

Information geometry provides the mathematical sciences with a new framework of analysis. It has emerged from the investigation of the natural differential geometric structure on manifolds of probability distributions, which consists of a Riemannian metric defined by the Fisher information and a one-parameter family of affine connections called the \\alpha-connections. The duality between the \\alpha-connection and the (-\\alpha)-connection together with the metric play an essential role in this geometry. This kind of duality, having emerged from manifolds of probability distributions, is ubiquitous, appearing in a variety of problems which might have no explicit relation to probability theory. Through the duality, it is possible to analyze various fundamental problems in a unified perspective. The first half of this book is devoted to a comprehensive introduction to the mathematical foundation of information geometry, including preliminaries from differential geometry, the geometry of manifolds or probability distributions, and the general theory of dual affine connections. The second half of the text provides an overview of wide areas of applications, such as statistics, linear systems, information theory, quantum mechanics, convex analysis, neural networks, and affine differential geometry. The book will serve as a suitable text for a topics course for advanced undergraduates and graduate students.