gebhart/patrepeval huggingface dataset:
Structure of a Covalent DNA Minor Groove Adduct with a Pyrrolobenzodiazepine Dimer: Evidence for Sequence-Specific Interstrand Crosslinking (1994)

The structure of the interstrand cross-linked adduct formed between a C8-C8'-linked pyrrolobenzodiazepine (PBD) dimer (DSB-120; 1,1'-(propane-1,3-diyldioxy)bis[(11aS)-7-methoxy-1,2,3,11a-t etrahydro-5H- pyrrolo[2,1-c][1,4]benzodiazepin-5-one]) and a self-complementary d(CICGATCICG)2 duplex has been determined from high-field 1D- and 2D-NMR data using a simulated annealing procedure. The refined structure supports earlier observations from solution NMR experiments and indicates that the covalently bound molecule spans six DNA base pairs in the minor groove, forming a symmetric cross-link between the spatially separated internal guanines and with active recognition of an embedded 5'-GATC bonding site. This result confirms that template-directed approaches are useful for the design of linked DNA-interactive PBD dimers with viable DNA cross-linking potential. Further, head-to-head connection of the PBD moieties results in an overall retention of 5'-GA bonding site preference for each alkylating PBD subunit. Structural analysis indicates that cross-link formation results in a localized perturbation of the DNA duplex, attributable in part to a mutual reduction in dynamic mobility or "covalent clamping" within the Gua4-Cyt7 base tract. However, ligand-induced distortion is confined to the Cyt7 and Ino8 residues on each strand. The Gua(N2)-Gua(N2) cross-link is stabilized by two directed H-bonds from the formed animal residues to N3 acceptor atoms of adenine bases on the 3'-side of each covalently modified guanine. Evidence for sequence-specific cross-linking with DSB-120 is provided by extended modeling studies which suggest that recognition of the favored d(.GATC.) motif is dominated by van der Waals steric factors, although electrostatic and H-bonded interaction terms also play a key role. This conclusion supports recent covalent footprinting studies revealing that this PBD dimer shows a selectivity for embedded base sequences of the type 5'-(pu/py)GATC(py/pu).
Metal-insulator transition and electrically driven memristive characteristics of SmNiO3 thin films (2011)

The correlated oxide SmNiO3 (SNO) exhibits an insulator to metal transition (MIT) at 130 °C in bulk form. We report on synthesis and electron transport in SNO films deposited on LaAlO3 (LAO) and Si single crystals. X-ray diffraction studies show that compressively strained single-phase SNO grows epitaxially on LAO while on Si, mixed oxide phases are observed. MIT is observed in resistance-temperature measurements in films grown on both substrates, with charge transport in-plane for LAO/SNO films and out-of-plane for Si/SNO films. Electrically driven memristive behavior is realized in LAO/SNO films, suggesting that SNO may be relevant for neuromorphic devices.
Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17 (2007)

Cleavage and release (shedding) of membrane proteins is a critical regulatory step in many normal and pathological processes. Evidence suggests that the antiaging transmembrane protein Klotho (KL) is shed from the cell surface by proteolytic cleavage. In this study, we attempted to identify the enzymes responsible for the shedding of KL by treating KL-transfected COS-7 cells with a panel of proteinase inhibitors and measuring cleavage products by Western blot. We report that metalloproteinase inhibitors, including EDTA, EGTA, and TAPI-1, inhibit the shedding of KL, whereas insulin increases shedding. The effects of the inhibitors in KL-transfected COS-7 cells were repeated in studies on rat kidney slices ex vivo, which validates the use of COS-7 cells as our model system. Tissue inhibitor of metalloproteinase (Timp)-3 effectively inhibits KL cleavage, whereas Timp-1 and Timp-2 do not, a profile that indicates the involvement of members of the A Desintegrin and Metalloproteinase (ADAM) family. Cotransfection of KL with either ADAM10 or ADAM17 enhances KL cleavage, whereas cotransfection of KL with small interference RNAs specific to ADAM10 and ADAM17 inhibits KL secretion. These results indicate that KL shedding is mediated mainly by ADAM10 and ADAM17 in KL-transfected COS-7 cells. The effect of insulin is abolished when ADAM10 or ADAM17 are silenced. Furthermore, we demonstrate that the effect of insulin on KL shedding is inhibited by wortmannin, showing that insulin acts through a PI3K-dependent pathway. Insulin enhances KL shedding without increasing ADAM10 and ADAM17 mRNA and protein levels, suggesting that it acts by stimulating their proteolytic activities.
Effects of treatment on outcome in mildly symptomatic patients with ischemia during daily life. The Atenolol Silent Ischemia Study (ASIST) (1994)

Atenolol treatment reduced daily life ischemia and was associated with reduced risk for adverse outcome in asymptomatic and mildly symptomatic patients compared with placebo.
An essential role in liver development for transcription factor XBP-1 (2000)

XBP-1 is a CREB/ATF family transcription factor highly expressed in hepatocellular carcinomas. Here we report that XBP-1 is essential for liver growth. Mice lacking XBP-1 displayed hypoplastic fetal livers, whose reduced hematopoiesis resulted in death from anemia. Nevertheless, XBP-1-deficient hematopoietic progenitors had no cell-autonomous defect in differentiation. Rather, hepatocyte development itself was severely impaired by two measures: diminished growth rate and prominent apoptosis. Specific target genes of XBP-1 in the liver were identified as alphaFP, which may be a regulator of hepatocyte growth, and three acute phase protein family members. Therefore, XBP-1 is a transcription factor essential for hepatocyte growth.
The responses of cells to electrical fields: a review. (1985)

The application of DC electric fields to cells has a long and contentious history. The interpretation of the response of cells to such fields was hampered by lack of adequate recording technique, contamination of cultures by electrode products, uncertainty about the magnitude of fields, and sometimes by the complexity of the biological system under study. Nevertheless, when Jaffe and Nuccitelli (12) reviewed the literature in 1977, they found eight reliable reports of the response of plant cells to applied fields and four of animal cells. Since then, several laboratories have applied electrical fields to isolated cells in culture and recorded the responses on film or video tape so that responses could be characterized carefully and the threshold field strengths established. In these later studies, the size and direction of the fields are known unambiguously and possible artifacts such as electrode products, nutrient gradients, flow effects, and temperature changes are controlled.
BESS: a source structure that fully suppresses the floating body effects in SOI CMOSFETs (2002)

The floating body effects in SOI CMOSFETs are fully suppressed by a bipolar embedded source structure (BESS) just beneath the n/sup +/ source junction. In this structure, a recombination center, or collector, is formed based on the solid-phase epitaxial mechanism of the Si-implanted SOI layer. The source-drain breakdown voltage of a device with this structure is the same as that of a bulk device, but with a remarkable improvement in the drain-induced barrier-lowering properties.
Doppler flow imaging of cytoplasmic streaming using spectral domain phase microscopy (2006)

Spectral domain phase microscopy (SDPM) is a function extension of spectral domain optical coherence tomography. SDPM achieves exquisite levels of phase stability by employing common-path interferometry. We discuss the theory and limitations of Doppler flow imaging using SDPM, demonstrate monitoring the thermal contraction of a glass sample with nanometer per second velocity sensitivity, and apply this technique to measurement of cytoplasmic streaming in an Amoeba proteus pseudopod. We observe reversal of cytoplasmic flow induced by extracellular CaCl2, and report results that suggest parabolic flow of cytoplasm in the A. proteus pseudopod.
Increased DNA microarray hybridization specificity using sscDNA targets (2005)

The use of amplified sscDNA may offer substantial advantages over IVT-based amplification methods, especially when very limited amounts of starting RNA are available. The use of sscDNA targets instead of cRNA targets appears to improve hybridization specificity.
<title>FLEXnav: a fuzzy logic expert dead-reckoning system for the Segway RMP</title> (2004)

Most mobile robots use a combination of absolute and relative sensing techniques for position estimation. Relative positioning techniques are generally known as dead-reckoning. Many systems use odometry as their only dead-reckoning means. However, in recent years fiber optic gyroscopes have become more affordable and are being used on many platforms to supplement odometry, especially in indoor applications. Still, if the terrain is not level (i.e., rugged or rolling terrain), the tilt of the vehicle introduces errors into the conversion of gyro readings to vehicle heading. In order to overcome this problem vehicle tilt must be measured and factored into the heading computation. A unique new mobile robot is the Segway Robotics Mobility Platform (RMP). This functionally close relative of the innovative Segway Human Transporter (HT) stabilizes a statically unstable single-axle robot dynamically, based on the principle of the inverted pendulum. While this approach works very well for human transportation, it introduces as unique set of challenges to navigation equipment using an onboard gyro. This is due to the fact that in operation the Segway RMP constantly changes its forward tilt, to prevent dynamically falling over. This paper introduces our new Fuzzy Logic Expert rule-based navigation (FLEXnav) method for fusing data from multiple gyroscopes and accelerometers in order to estimate accurately the attitude (i.e., heading and tilt) of a mobile robot. The attitude information is then further fused with wheel encoder data to estimate the three-dimensional position of the mobile robot. We have further extended this approach to include the special conditions of operation on the Segway RMP. The paper presents experimental results of a Segway RMP equipped with our system and running over moderately rugged terrain.
Rheology of End-Tethered Polymer Layered Silicate Nanocomposites (1997)

The rheology of end-tethered polymer layered silicate nanocomposites is investigated using linear viscoelastic measurements in oscillatory shear with small strain amplitudes. Two systems consisting of poly(ε-caprolactone) and nylon-6 with varying amounts of layered silicate (montmorillonite) are examined. The storage (G‘) and loss (G‘‘) moduli increase at all frequencies with increasing silicate loading, consistent with previous findings with conventionally filled polymer systems. However, the power-law dependence of G‘ and G‘‘ in the terminal zone is different from that observed in homopolymers and decreases with increasing silicate loading. At low frequencies the rheological response becomes almost invariant with frequency, suggestive of a solid-like response. Comparisons are drawn with rheology of other intrinsically anisotropic materials, and an attempt is made to explain phenomenologically their rich-rheological behavior.
Identification of Contact Residues and Definition of the CAR-Binding Site of Adenovirus Type 5 Fiber Protein (2000)

The binding of adenovirus (Ad) fiber knob to its cellular receptor, the coxsackievirus and Ad receptor (CAR), promotes virus attachment to cells and is a major determinant of Ad tropism. Analysis of the kinetics of binding of Ad type 5 (Ad5) fiber knob to the soluble extracellular domains of CAR together (sCAR) and each immunoglobulin (Ig) domain (IgV and IgC2) independently by surface plasmon resonance demonstrated that the IgV domain is necessary and sufficient for binding, and no additional membrane components are required to confer high-affinity binding to Ad5 fiber knob. Four Ad5 fiber knob mutations, Ser408Glu and Pro409Lys in the AB loop, Tyr477Ala in the DG loop, and Leu485Lys in beta strand F, effectively abolished high-affinity binding to CAR, while Ala406Lys and Arg412Asp in the AB loop and Arg481Glu in beta strand E significantly reduced the level of binding. Circular dichroism spectroscopy showed that these mutations do not disorder the secondary structure of the protein, implicating Ser408, Pro409, Tyr477, and Leu485 as contact residues, with Ala406, Arg412, and Arg481 being peripherally or indirectly involved in CAR binding. The critical residues have exposed side chains that form a patch on the surface, which thus defines the high-affinity interface for CAR. Additional site-directed mutagenesis of Ad5 fiber knob suggests that the binding site does not extend to the adjacent subunit or toward the edge of the R sheet. These findings have implications for our understanding of the biology of Ad infection, the development of novel Ad vectors for targeted gene therapy, and the construction of peptide inhibitors of Ad infection.
Potential and limitations of bacterial-mediated cancer therapy (2007)

Bacterial-based tumor-targeted therapy is an area of growing interest and holds promise for the treatment of solid tumors. Upon systemic administration, various types of non-pathogenic obligate anaerobes and facultative anaerobes have been shown to infiltrate and selectively replicate within solid tumors. The tumor specificity is based upon the unique physiology of solid tumors, which is often characterized by regions of hypoxia and necrosis. Prokaryotic vectors can be safely administered and their potential to deliver therapeutic proteins has been demonstrated in a variety of preclinical models. Although the amount of clinical experience with bacterial vectors is limited to date, the available data clearly demonstrated the feasibility of bacterial-mediated therapy in humans. There are several issues however that are still unknown and remain major challenges. In this review, using Clostridium and modified Salmonella as prototypical agents, we will discuss the major advantages, challenges and shortcomings of bacterial systems for tumor-specific therapy. In addition, we will highlight the requirements needed to advance the approach into clinical trials.
In situ detection of microRNAs146b, 221 and 222 in human carcinoma tissues reveals tumor-type specific expression patterns. (2007)

1780 MicroRNAs (miRs) are transcribed from non-protein-encoding genes that regulate the post-transcriptional fate of other, protein-encoding mRNAs. Overexpression of miR146b, miR221 and miR222 has been reported in papillary thyroid carcinomas (PTC). In the present study, we sought to determine the expression of these miRs at the histological level in thyroid cancer. A total of 87 different archival cancer specimens, including 65 thyroid carcinomas (26 PTC, 25 medullary [MTC], 14 anaplastic [ATC]), were examined on paraffin sections in comparison to matched normal tissues and clinicopathological parameters. The expression of miRs 146b, 221 and 222 was assessed by in situ hybridization (ISH) with cocktails of DIG-labeled oligonucleotide probes complementary to each miR. Semiquantitative RT-PCR for the same targets was performed for a subset of 25 tumor/normal pairs and showed concordant results with ISH in all but one case. In normal epithelia (thyroid, breast, colon, stomach), faint positive cytoplasmic signal of all three miRs was observed in limited cases (10 - 12%) and cells/case (
MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines (2011)

Oil-in-water adjuvants have been shown to improve immune responses against pandemic influenza vaccines as well as reduce the effective vaccine dose, increasing the number of doses available to meet global vaccine demand. Here, we use genome fragment phage display libraries and surface plasmon resonance to elucidate the effects of MF59 on the quantity, diversity, specificity, and affinity maturation of human antibody responses to the swine-origin H1N1 vaccine in different age groups. In adults and children, MF59 selectively enhanced antibody responses to the hemagglutinin 1 (HA1) globular head relative to the more conserved HA2 domain in terms of increased antibody titers as well as a more diverse antibody epitope repertoire. Antibody affinity, as inferred by greatly diminished (≥10-fold) off-rate constants, was significantly increased in toddlers and children who received the MF59-adjuvanted vaccine. Moreover, MF59 also improved antibody affinity maturation after each sequential vaccination against avian H5N1 in adults. For both pandemic influenza vaccines, there was a close correlation between serum antibody affinity and virus-neutralizing capacity. Thus, MF59 quantitatively and qualitatively enhances functional antibody responses to HA-based vaccines by improving both epitope breadth and binding affinity, demonstrating the added value of such adjuvants for influenza vaccines.
Electroforming, Switching and Memory Effects in Oxide Thin Films (1977)

Experiments on electroforming of Metal‐Oxide‐Metal thin film sandwiches which have been electroformed to exhibit voltage‐controlled negative resistance are summarized and an outline of recent evidence in favour of localized or filamentary conduction is given. A similar review is given of the experiments on oxide sandwich structures which have been formed to exhibit current‐controlled negative resistance or threshold switching and memory switching. Current theories are reviewed briefly. Finally oxide memory devices are compared with those based upon the chalcogenide glasses.
Evidence that hsp90 Is Involved in the Altered Interactions ofAcanthamoeba castellaniiVariants with Bacteria (2004)

There are many similarities between the interactions of environmental protozoa with pathogenic bacterial species and those observed in mammalian macrophages. Since single-celled protozoa predate mammalian hosts, it is likely that interactions in environmental biofilms have selected for many of the bacterial virulence mechanisms responsible for human disease. In order to better understand bacterial-phagocyte interactions, we developed a selection for Acanthamoeba castellanii variants that are more resistant to killing by bacterial pathogens. We identified four amoebal clones that display decreased phagocytosis of bacteria but no difference in uptake of latex beads compared to wild-type amoebae. These amoebal variants display differences in cellular morphology, partial resistance to killing by bacteria, more bactericidal activity, and higher frequencies of lysosome fusion with the bacterial vacuole. Three proteins are present at lower levels in these variants than in wild-type amoebae, and matrix-assisted laser desorption ionization-time of flight mass spectrometry allowed identification of two of them as actin and hsp90. We found that specific inhibitors of hsp90 produce a similar phenotypic effect in macrophages. These data suggest that hsp90 plays a role in phagocytic and, possibly, bactericidal pathways that affect interactions of phagocytic cells with bacteria.
Insights into the genome evolution of Yersinia pestis through whole genome comparison with Yersinia pseudotuberculosis (2004)

Yersinia pestis, the causative agent of plague, is a highly uniform clone that diverged recently from the enteric pathogen Yersinia pseudotuberculosis. Despite their close genetic relationship, they differ radically in their pathogenicity and transmission. Here we report the complete genomic sequence of Y. pseudotuberculosis IP32953 and its use for detailed genome comparisons to available Y. pestis sequences. Analyses of identified differences across a panel of Yersinia isolates from around the world reveals 32 Y. pestis chromosomal genes that, together with the two Y. pestis-specific plasmids, represent the only new genetic material in Y. pestis acquired since the divergence from Y. pseudotuberculosis. In contrast, 149 new pseudogenes (doubling the previous estimate) and 317 genes absent from Y. pestis were detected, indicating that as many as 13% of Y. pseudotuberculosis genes no longer function in Y. pestis. Extensive IS-mediated genome rearrangements and reductive evolution through massive gene loss, resulting in elimination and modification of pre-existing gene expression pathways appear to be more important than acquisition of new genes in the evolution of Y. pestis. These results provide a sobering example of how a highly virulent epidemic clone can suddenly emerge from a less virulent, closely related progenitor.
Nanoscale Metal–Organic Framework for Highly Effective Photodynamic Therapy of Resistant Head and Neck Cancer (2014)

Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor localization of a photosensitizer followed by light activation to generate cytotoxic reactive oxygen species (e.g., (1)O2). Here we report the rational design of a Hf-porphyrin nanoscale metal-organic framework, DBP-UiO, as an exceptionally effective photosensitizer for PDT of resistant head and neck cancer. DBP-UiO efficiently generates (1)O2 owing to site isolation of porphyrin ligands, enhanced intersystem crossing by heavy Hf centers, and facile (1)O2 diffusion through porous DBP-UiO nanoplates. Consequently, DBP-UiO displayed greatly enhanced PDT efficacy both in vitro and in vivo, leading to complete tumor eradication in half of the mice receiving a single DBP-UiO dose and a single light exposure. NMOFs thus represent a new class of highly potent PDT agents and hold great promise in treating resistant cancers in the clinic.
Achieving network on chip fault tolerance by adaptive remapping (2009)

This paper investigates achieving fault tolerance by adaptive remapping in the context of networks on chip. The problem of dynamic application remapping is formulated and an efficient algorithm is proposed to address single and multiple PE failures. The new algorithm can be used to dynamically react and recover from PE failures in order to maintain system functionality. The quality of results is similar to that achieved using simulated annealing but in significantly shorter runtimes.
Constitutive expression of IL‐1β, M‐CSF and c‐fms during the myeloid blastic phase of chronic myelogenous leukaemia (1992)

During the myeloid blast crisis (BC) of chronic myelogenous leukaemia (CML) non-random additional chromosome abnormalities occur in over 80% of patients. However, these cytogenetic changes have been reported to precede the clinical signs of CML-BC by several months to years suggesting that other biological events may participate in the multistep process of acute transformation of CML. The autocrine production of growth factors has been recently shown to occur in several haematological malignancies and particularly in acute myeloblastic leukaemia (AML). In the present report we demonstrate that IL-1 beta gene is expressed in almost all cases of CML in myeloid blast crisis. The secretion of IL-1 from CML blasts in culture supernatants was confirmed in all five of the patients we studied. A high proportion of cases showed constitutive expression of the M-CSF gene and many of the same patients often had a simultaneous co-expression of the proto-oncogene c-fms which encodes for the M-CSF receptor. After exposure of leukaemic cells to phorbol myristate acetate (PMA), release of M-CSF protein was documented in three of five patients studied. No significant interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF), was detected in these patients demonstrating that a different pattern of growth factors secretion exist in AML and CML, where distinct molecular events are likely involved in the control of leukaemic proliferation.