gebhart/patrepeval huggingface dataset:
Recognition of occluded patterns: a neural network model (2000)

This paper proposes a hypothesis explaining why a pattern is easier to be recognized when the occluding objects are visible. A neural network model is constructed based on the hypothesis and is demonstrated that the model responds to occluded patterns in a similar way as human beings. The visual system extracts various visual features from the input pattern and then recognizes it. If the occluding objects are invisible, the visual system will have difficulty in distinguishing which features are relevant to the original pattern and which are newly generate by the occlusion. If the occluding objects are visible, however, the visual system can easily discriminate relevant from irrelevant features and recognize the occluded pattern correctly. The proposed model is an extended version of the neocognitron model. The activity of the feature-extracting S-cells whose receptive fields cover the occluding objects is suppressed in the lowest stage of the hierarchical network.
Myasthenia Gravis (1994)

Twenty years ago, the discovery of a deficit of acetylcholine receptors at the neuromuscular junctions of patients with myasthenia gravis1 and the development of an animal model of the disease2 shed new light on a disorder that was first described clinically 300 years earlier by the great physiologist Thomas Willis3. During the past two decades, remarkable progress has been made in our understanding of myasthenia gravis, and the new knowledge has been applied directly to the clinical diagnosis and treatment of this formerly grave disease. Myasthenia gravis is undoubtedly the most thoroughly understood of all human autoimmune diseases and . . .
Haplotype and interspersion analysis of the FMR1 CGG repeat identifies two different mutational pathways for the origin of the fragile X syndrome (1996)

To understand the origins of the fragile X syndrome and factors predisposing alleles to instability and hyperexpansion, we have compared the haplotype (using markers FRAXAC1, FRAXAC2, and DXS548) and AGG interspersion patterns of the FMR1 CGG repeat for 214 normal and 16 premutation chromosomes. Association testing between interspersion pattern and haplotype reveals a highly significant (P < 0.002) non-random distribution, indicating that all three markers are useful in phylogenetic reconstruction of mutational change. Parsimony analysis of the FMR1 CGG repeat substructure predicts that loss of AGG interruptions has occurred independently on many haplotypes associated with the fragile X syndrome, partially explaining the haplotype diversity of this disease. Among haplotypes found in linkage disequilibrium with the fragile X mutation, two different modes of mutation and predisposition to instability have been identified. One pathway has involved the frequent and recurrent loss of AGG interruptions from rare asymmetrical ancestral array structures. Intergenerational transmission studies suggest that these predisposed chromosomes progress relatively rapidly to the disease state. In contrast, the second mutational pathway involves a single haplotype which has maintained two AGG interruptions. Parsimony analysis of CGG repeat substructure within this haplotype suggests that larger alleles have been generated by gradual increments of CGG repeats distal to the most 3' interruption. Pedigree analysis of the intergenerational stability of alleles of this haplotype confirms a gradual progression toward instability thresholds. As a result, a large reservoir of chromosomes carrying large repeats on this haplotype exists. These chromosomes are predisposed to disease. The present data support a model in which there are at least two different mutational pathways predisposing alleles to instability and hyperexpansion associated with the fragile X syndrome.
Lipid Lowering by Simvastatin Induces Regression of Human Atherosclerotic Lesions (2002)

The present study demonstrates that maintained lipid-lowering therapy with simvastatin is associated with significant regression of established atherosclerotic lesions in humans. Our observations indicate that lipid-lowering therapy is associated with sustained vascular remodeling and emphasize the need for longer-term treatment.
The Importance of Thermophilic Bacteria in Biotechnology (1985)

(1985). The Importance of Thermophilic Bacteria in Biotechnology. Critical Reviews in Biotechnology: Vol. 3, No. 1, pp. 39-108.
Site-Specific Antibody–Drug Conjugation through Glycoengineering (2014)

Antibody-drug conjugates (ADCs) have been proven clinically to be more effective anti-cancer agents than native antibodies. However, the classical conjugation chemistries to prepare ADCs by targeting primary amines or hinge disulfides have a number of shortcomings including heterogeneous product profiles and linkage instability. We have developed a novel site-specific conjugation method by targeting the native glycosylation site on antibodies as an approach to address these limitations. The native glycans on Asn-297 of antibodies were enzymatically remodeled in vitro using galactosyl and sialyltransferases to introduce terminal sialic acids. Periodate oxidation of these sialic acids yielded aldehyde groups which were subsequently used to conjugate aminooxy functionalized cytotoxic agents via oxime ligation. The process has been successfully demonstrated with three antibodies including trastuzumab and two cytotoxic agents. Hydrophobic interaction chromatography and LC-MS analyses revealed the incorporation of ~1.6 cytotoxic agents per antibody molecule, approximating the number of sialic acid residues. These glyco-conjugated ADCs exhibited target-dependent antiproliferative activity toward antigen-positive tumor cells and significantly greater antitumor efficacy than naked antibody in a Her2-positive tumor xenograft model. These findings suggest that enzymatic remodeling combined with oxime ligation of the native glycans of antibodies offers an attractive approach to generate ADCs with well-defined product profiles. The site-specific conjugation approach presented here provides a viable alternative to other methods, which involve a need to either re-engineer the antibody sequence or develop a highly controlled chemical process to ensure reproducible drug loading.
Microengineering of Cellular Interactions (2000)

Tissue function is modulated by an intricate architecture of cells and biomolecules on a micrometer scale. Until now, in vitro cellular interactions were mainly studied by random seeding over homogeneous substrates. Although this strategy has led to important discoveries, it is clearly a nonoptimal analog of the in vivo scenario. With the incorporation--and adaptation--of microfabrication technology into biology, it is now possible to design surfaces that reproduce some of the aspects of that architecture. This article reviews past research on the engineering of cell-substrate, cell-cell, and cell-medium interactions on the micrometer scale.
Assessment of renal function in recently admitted critically ill patients with normal serum creatinine (2005)

In recently admitted critically ill patients with normal serum creatinine, serum creatinine had a low sensitivity for detection of renal dysfunction. Furthermore, the Cockcroft-Gault and MDRD equations were not adequate in assessing renal function.
Long range surface plasmon fluorescence spectroscopy (2006)

Surface plasmon modes, resonantly excited at the two sides of an ultrathin (noble) metal layer in contact with two (nearly) identical dielectric media interact via the overlap of their electromagnetic fields resulting in two new coupled modes, i.e., a short range and a long range surface plasmon (LRSP), respectively. The authors demonstrate that both the enhanced optical field of the LRSP wave at the metal/dielectric interface as well as its increased (evanescent) penetration depth reaching farther into the analyte solution can be used for significant enhancements when using LRSP optics in a fluorescence spectroscopic mode of operation. They demonstrate this for the detection of fluorescence intensities from chromophore labeled proteins bound to the sensor surface matrix.
Expression of iron-regulated outer membrane proteins by porcine strains of Pasteurella multocida. (1995)

The outer membrane protein (OMP) profiles of two strains of capsular type A Pasteurella multocida isolated from the lungs of pigs with enzootic pneumonia were studied. Sarkosyl extracted OMPs from P. multocida grown under iron-restricted and iron-replete conditions were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Results showed that the iron-regulated outer membrane proteins (IROMPs) with molecular masses of 74 kDa, 94 kDa, 99 kDa and 109 kDa were expressed by strain A52, while 74 kDa, 82 kDa, 94 kDa and 99 kDa IROMPs were expressed by strain B80. Swine immune sera, obtained from pigs which were first immunized with a polyvalent P. multocida type A and type D bacterin and subsequently challenged with type A strain of P. multocida, contained antibodies against the IROMPs. These antibodies cross-reacted with the IROMPs expressed by avian strain P1059 of P. multocida. Convalescent-phase serum obtained from turkeys which survived fowl cholera, also cross-reacted with the IROMPs from porcine strains of P. multocida. These results suggested that IROMPs from porcine and avian strains of P. multocida may share common epitopes that were recognized by swine immune serum as well as turkey convalescent-phase serum.
The Cotranslational Maturation of the Type I Membrane Glycoprotein Tyrosinase: The Heat Shock Protein 70 System Hands Off to the Lectin-based Chaperone System (2005)

The maturation of eukaryotic secretory cargo initiates cotranslationally and cotranslocationally as the polypeptide chain emerges into the endoplasmic reticulum lumen. Here, we characterized the cotranslational maturation pathway for the human type I membrane glycoprotein tyrosinase. To recapitulate the cotranslational events, including glycosylation, signal sequence cleavage, chaperone binding, and oxidation, abbreviated transcripts lacking a stop codon were in vitro translated in the presence of semipermeabilized melanocyte membranes. This created a series of ribosome/translocon-arrested chains of increasing lengths, simulating intermediates in the cotranslational folding process. Initially, nascent chains were found to associate with the heat shock protein (Hsp) 70 family member BiP. As the nascent chains elongated and additional glycans were transferred, BiP binding rapidly decreased and the lectin-based chaperone system was recruited in its place. The lectin chaperone calnexin bound to the nascent chain after the addition of two glycans, and calreticulin association followed upon the addition of a third. The glycan-specific oxidoreductase ERp57 was cross-linked to tyrosinase when calnexin and calreticulin were associated. This timing coincided with the formation of disulfide bonds within tyrosinase and the cleavage of its signal sequence. Therefore, tyrosinase maturation initiates cotranslationally with the Hsp70 system and is handed off to the lectin chaperone system that first uses calnexin before calreticulin. Interestingly, divergence in the maturation pathways of wild-type and mutant albino tyrosinase can already be observed for translocon-arrested nascent chains.
Synergistic Effects of IL-12 and IL-18 in Skewing Tumor-Reactive T-Cell Responses Towards a Type 1 Pattern (2005)

We have previously described the antitumor reactivity of tumor-draining lymph node (TDLN) cells after secondary activation with antibodies. In this report, we examined the effects of interleukin (IL)-12 and IL-18 on modulating the immune function of antibody-activated murine TDLN cells. TDLN cells were activated with anti-CD3/anti-CD28 monoclonal antibody followed by stimulation with IL-12 and/or IL-18. IL-18 in combination with IL-12 showed a synergistic effect in augmenting IFNgamma and granulocyte macrophage colony-stimulating factor secretion, whereas IL-18 alone had minimal effect. Concurrently, IL-18 prevented IL-12-stimulated TDLN cells from producing IL-10. The IL-12/IL-18-cultured TDLN cells therefore manifested cytokine responses skewed towards a Th1/Tc1 pattern. IL-12 and IL-18 stimulated CD4(+) TDLN cells and enhanced IFNgamma production by CD4(+) cells to a greater extent than by CD8(+) cells. Use of NF-kappaB p50(-/-) TDLN cells suggested the involvement of NF-kappaB in the IL-12/IL-18 polarization effect. Furthermore, a specific NF-kappaB inhibitor significantly suppressed IL-12/IL-18-induced IFNgamma secretion, thus confirming the requirement for NF-kappaB activation in IL-12/IL-18 signaling. In adoptive immunotherapy, IL-12- and IL-18-cultured TDLN cells infiltrated pulmonary tumor nodules and eradicated established tumor metastases more efficiently than T cells generated with IL-12 or IL-18 alone. Antibody depletion revealed that both CD4(+) and CD8(+) cells were involved in the tumor rejection induced by IL-12/IL-18-cultured TDLN cells. These studies indicate that IL-12 and IL-18 can be used to generate potent CD4(+) and CD8(+) antitumor effector cells by synergistically polarizing antibody-activated TDLN cells towards a Th1 and Tc1 phenotype.
IL-6 involvement in epithelial cancers (2007)

In this issue of the JCI, two reports provide intriguing new information on the role of the inflammatory cytokine IL-6 in breast and lung cancer. The study by Sansone et al. implicates IL-6 in the instigation of malignant properties in breast cancer stem cells (see the related article beginning on page 3988). The study by Gao et al. identifies mutant variants of EGFR as inducers of IL-6 in lung adenocarcinomas (see the related article beginning on page 3846). These studies add to our understanding of potential roles for IL-6 in cancer and further motivate investigations of IL-6-targeted chemotherapeutics.
Humoral Immune Responses in the Hantavirus Cardiopulmonary Syndrome (2000)

The immunologic responses that mediate viral clearance of and recovery from hantavirus cardiopulmonary syndrome (HCPS) due to Sin Nombre (SN) virus are unknown. Serial serum samples from 26 patients with acute SN virus infection were tested for IgG, IgA, and IgM reactivity to recombinant viral nucleocapsid (N) and glycoprotein G1 antigens by a novel strip immunoblot assay. The titers of antibodies capable of neutralizing SN virus in vitro also were determined for each sample. At admission, patients with severe disease had lower titers of IgG antibodies to SN virus N antigen (P<.033) and lower neutralizing antibody titers (P<3.4x10-5), compared with patients with mild disease. These data suggest that a strong neutralizing antibody response may be a predictor of effective clearance of and recovery from SN virus infection and raise the possibility that passive immunotherapy may be useful in HCPS.
A monoclonal antibody against 2,2,7‐trimethylguanosine that reacts with intact, class U, small nuclear ribonucleoproteins as well as with 7‐methylguanosine‐capped RNAs (1987)

A hybridoma secreting a monoclonal antibody (H-20) that recognizes the 2,2,7-trimethylguanosine(m3G)-containing cap structure of U snRNAs was derived from a mouse which was immunized with a m3G-containing human serum albumin conjugate. The antibody specifically reacts with intact small nuclear ribonucleoprotein particles, U snRNPs, and allows the snRNPs U1 to U6 to be isolated in one step from nuclear extracts of eucaryotic cells by affinity chromatography on a preparative scale. Antibody-bound snRNPs are desorbed from the affinity column by elution with excess of the cross-reactive nucleoside 7-methylguanosine (m7G), which guarantees maintenance of their native structure. The 20 affinity column also allows the snRNPs U1, U2 and U5 to be separated from U4/U6 RNPs by sequential elution of the particles with m7G under differential salt concentrations. As determined by competitive radioimmunoassay and protein-A--Sepharose immunoprecipitation, mAb H-20 crossreacts with intact m7G cap structures. In particular we could show that non-denatured m7G-capped SP6/beta-globin RNA was precipitated efficiently by the antibody while GpppG-capped or non-capped RNAs did not react. Thus the monoclonal antibody H-20 should have a wide application, not only for studying the molecular biology and immunology of the U snRNPs from diverse organisms, but also for the characterization and isolation of m7G-capped transcripts.
UBE1L2, a Novel E1 Enzyme Specific for Ubiquitin* (2007)

UBE1 is known as the human ubiquitin-activating enzyme (E1), which activates ubiquitin in an ATP-dependent manner. Here, we identified a novel human ubiquitin-activating enzyme referred to as UBE1L2, which also shows specificity for ubiquitin. The UBE1L2 sequence displays a 40% identity to UBE1 and also contains an ATP-binding domain and an active site cysteine conserved among E1 family proteins. UBE1L2 forms a covalent link with ubiquitin in vitro and in vivo, which is sensitive to reducing conditions. In an in vitro polyubiquitylation assay, recombinant UBE1L2 could activate ubiquitin and transfer it onto the ubiquitin-conjugating enzyme UbcH5b. Ubiquitin activated by UBE1L2 could be used for ubiquitylation of p53 by MDM2 and supported the autoubiquitylation of the E3 ubiquitin ligases HectH9 and E6-AP. The UBE1L2 mRNA is most abundantly expressed in the testis, suggesting an organ-specific regulation of ubiquitin activation.
Instrumentation for trace detection of high explosives (2004)

There is at present an urgent need for trace detection of high explosives, with applications to screening of people, packages, luggage, and vehicles. A great concern, because of recent terrorist activities, is for the development of methods that might allow detection and identification of explosives at a stand off distance. Nearly every analytical chemical method has been or is being applied to this problem. This review outlines the properties of explosives that might be utilized in detection schemes, discusses sampling issues, presents recent method developments with particular attention to detection limits, speed of analysis, and portability, and looks towards future developments.
Binding of progastrin fragments to the 78 kDa gastrin‐binding protein (1995)

The non-selective gastrin/cholecystokinin receptor antagonists proglumide and benzotript inhibit colon carcinoma cell proliferation by binding to the 78 kDa gastrin-binding protein (GBP) (Baldwin, Proc. Natl. Acad. Sci. USA, 91 (1994) 7593-7597). However, although most colon carcinoma cell lines synthesize progastrin, production of mature amidated gastrin17 has not been observed. In order to define the structural requirements for the binding of gastrin to the GBP the affinities of various fragments of amidated and C-terminally extended gastrin17 for the GBP have been measured. The results indicate that the GBP recognizes both N- and C-termini of gastrin17. Moreover since C-terminal amidation is not a prerequisite for binding of gastrin to the GBP, the GBP is a potential target for the autocrine effects of progastrin.
A Biologist's Guide to Analysis of DNA Microarray Data (2002)

Most contemporary data analysis methods are discussed in chapters 3-8, in which the underlying principles are illustrated with vivid and simple examples. In chapter 3, Knudsen describes the basic data analysis methods, including scaling the measurements in the sample and the control, calculating the change in expression level of a gene and determining the significance of the expression level of a gene by using student’s t-tests, ANOVA or nonparametric tests. Potential problems, such as outliers, and multiple testing are discussed. Chapters 4-8 introduce various data processing and mining methods: principal component analysis for dimensionality reduction; cluster analysis, including hierarchical clustering, K-means clustering and selforganizing maps; various distance measures and their effects on data clustering; normalization methods to correct systematic biases; mining functions of orphan proteins and regulatory relationships between genes; reverse engineering of regulatory networks by time-series and steadystate approaches; constructing molecular classifiers, including nearest neighbor, neural networks and support vector machines. The constraints of these data analysis methods are emphasized and discussed in detail. This is very helpful for those without a strong background in statistics, as the limitations of statistical analysis methods are often overlooked.
Sumatriptan (all routes of administration) for acute migraine attacks in adults - overview of Cochrane reviews (2014)

Sumatriptan is an effective abortive treatment for acute migraine attacks, but is associated with increased adverse events relative to placebo. The route of administration influences efficacy, particularly within the first hour after administration. Subcutaneous sumatriptan shows the greatest efficacy in terms of pain relief, but at the expense of relatively high levels of adverse events, and with a high financial cost compared with other routes. Information about the relative efficacy of the different routes of administration for different outcomes should help to inform decisions about the suitability of sumatriptan as a migraine treatment, as well as about the most appropriate way to administer the treatment for individual patients.
Fractured Fairytales: The Failed Social License for Unconventional Oil and Gas Development (2013)

almost entirely natural gas-fired, which is also expediting the retirement of
Production of influenza virus in serum-free mammalian cell cultures. (1999)

Human influenza viruses are routinely isolated and grown in a variety of mammalian cell substrates. However, influenza viruses for use as inactivated vaccine are still produced in embryonated eggs. Using a perfusion culture-based bioreactor process using serum-free medium, both human and equine influenza viruses of different types and subtypes could be produced to high titres. Classical DEAE-dextran microcarriers were found to be more suitable than polyester sponge carriers for virus production. In addition, MDCK cells grown in serum-free medium were further validated as the most suitable cell substrate compared to Vero and BHK-21 C13 cells for large scale virus production of influenza virus. Finally, to minimize potential contamination by adventitious agents, it was demonstrated that a new serum-free medium in which all animal-derived products are replaced by a plant extract, efficiently supports the growth of MDCK cells as well as the production of influenza virus in the presence of trypsin when using the perfusion bioreactor process.
Spatially Resolved Dynamics of cAMP and Protein Kinase A Subunits in Aplysia Sensory Neurons (1993)

Cyclic adenosine monophosphate (cAMP)-dependent protein kinase, labeled with fluorescein and rhodamine on the catalytic and regulatory subunits, respectively, was injected into Aplysia sensory neurons either in culture or in intact cell clusters. Energy transfer between the subunits, a measure of cytosolic cAMP concentration ([cAMP]), and compartmentation of the dissociated subunits were monitored by confocal fluorescence microscopy. Bath application of serotonin produced a much greater elevation of [cAMP] in the processes than in the central bodies of the neurons. The resulting gradients must drive a sizable centripetal flux of cAMP because direct microinjection of cAMP showed that it diffused readily. Perinuclear increases in [cAMP] slowly caused the translocation of the freed catalytic subunit into the nucleus to an extent proportional to the percentage of its dissociation from the regulatory subunit.