gebhart/patrepeval huggingface dataset:
The electrical conductivity of human cerebrospinal fluid at body temperature (1997)

The electrical conductivity of human cerebrospinal fluid (CSF) from seven patients was measured at both room temperature (25 degrees C) and body temperature (37 degrees C). Across the frequency range of 10 Hz-10 kHz, room temperature conductivity was 1.45 S/m, but body temperature conductivity was 1.79 S/m, approximately 23% higher. Modelers of electrical sources in the human brain have underestimated human CSF conductivity by as much as 44% for nearly two decades, and this should be corrected to increase the accuracy of source localization models.
Hyperthermia mediated liposomal drug delivery (2006)

Drug delivery systems have been developed for cancer therapy in an attempt to increase the tumour drug concentration while limiting systemic exposure. Liposomes have achieved passive targeting of solid tumours through enhanced vascular permeability, which is greatly augmented by hyperthermia. However, anti-tumour efficacy has often been limited by slow release of bioavailable drug within the tumour. Local hyperthermia has become the most widely used stimulus for triggered release of liposomal drugs, through the use of specific lipids, polymers or other modifiers. A temperature-sensitive liposome containing doxorubicin has been shown to release 100% of contents through stabilized membrane pores within 10-20 s at 41 degrees C. This formulation has exhibited dramatic improvements in pre-clinical drug delivery and tumour regression and is now in clinical trials. Significantly, recent studies show that this liposome, in combination with local hyperthermia, exhibits vascular shutdown as a mechanism of anti-tumour effect that is not observed with free doxorubicin.
miRNAs in cancer: approaches, aetiology, diagnostics and therapy (2007)

MicroRNAs (miRNAs) are causing tremendous excitement in cancer research. MiRNAs are a large class of short non-coding RNAs that are found in many plants, animals and DNA viruses and often act to inhibit gene expression post-transcriptionally. Approximately 500 miRNA genes have been identified in the human genome. Their function is largely unknown, but data from worms, flies, fish and mice suggest that they have important roles in animal growth, development, homeostasis and disease. MiRNA expression profiles demonstrate that many miRNAs are deregulated in human cancers. MiRNAs have been shown to regulate oncogenes, tumour suppressors and a number of cancer-related genes controlling cell cycle, apoptosis, cell migration and anglogenesis. MiRNAs encoded by the mir-17-92 cluster have oncogenic potential and others may act as tumour suppressors. Some miRNAs and their target sites were found to be mutated in cancer. MiRNAs may have great diagnostic potential for human cancer and even mIRNA-based cancer therapies may be on the horizon.
Development of prophylactic vaccines for genital and neonatal herpes (2003)

Over five decades numerous conventional candidate live attenuated and killed vaccines have failed to prevent genital herpes in clinical trials. However, a vaccine consisting of recombinant glycoprotein D from herpes simplex virus (HSV)-2 and deacylated monophosphoryl lipid A adjuvant has recently shown partial efficacy against clinical disease transmitted from HSV-1 and -2 seronegative women (73-74%). Comparisons between the efficacy of this vaccine and previous failed candidates and their effects on the immune system should help guide development of better vaccines through selection of appropriate HSV proteins, adjuvants or cytokines and newer vaccine vectors, such as DNA vaccines, recombinant viral vaccines and specific HSV mutants.
Metabotropic Glutamate Receptor Subtypes 1 and 5 Are Activators of Extracellular Signal-Regulated Kinase Signaling Required for Inflammatory Pain in Mice (2001)

Metabotropic glutamate receptors are expressed abundantly in the spinal cord and have been shown to play important roles in the modulation of nociceptive transmission and plasticity. Most previous studies have focused on the group I metabotropic glutamate receptors (mGluR1 and mGluR5) and activation of phospholipase C signaling by these receptors in modulating nociception. Recently, it was shown that the extracellular signal-regulated kinases (ERKs)/mitogen-activated protein kinases are activated in spinal cord dorsal horn neurons in response to stimulation of nociceptors and that ERK signaling is involved in nociceptive plasticity. In the present studies, we sought to test the hypothesis that group I mGluRs modulate nociceptive transmission or plasticity via modulation of ERK signaling in dorsal horn neurons. We show that activation of mGluR1 and mGluR5 leads to activation of ERK1 and ERK2 in the spinal cord. Furthermore, we find that inflammation-evoked ERK activation, which is required for nociceptive plasticity, is downstream of mGluR1 and mGluR5. Finally, we show colocalization of group I mGluRs with activated ERK in dorsal horn neurons. These results show that mGluR1 and mGluR5 are activated in dorsal horn neurons in response to peripheral inflammation and that activation of these group I mGluRs leads to activation of ERK1 and ERK2, resulting in enhanced pain sensitivity.
Gene silencing with RNA interference in the human pathogenic fungus Aspergillus fumigatus (2004)

Aspergillus fumigatus is an opportunistic pathogenic fungus which causes fatal invasive aspergillosis among immunocompromised patients. To obtain a better understanding of the key elements involved in A. fumigatus virulence and to identify possible drug targets, it is necessary to be able to generate gene-deletion strains. Unfortunately, the molecular techniques available do not include a rapid method to disrupt and identify essential genes. RNA interference, a process in which the presence of double-stranded RNA homologous to a gene of interest results in specific degradation of the corresponding message, has been successfully tested on A. fumigatus. We have shown that expression of double stranded RNA corresponding to portions of the ALB1/PKSP and FKS1 genes results in reduced mRNA levels for those genes, with phenotypic consequences similar to that of gene disruption. The two genes could also be subjected to simultaneous interference through expression of chimeric double-stranded RNA. Use of RNA interference in Aspergillus will allow easier examination of the phenotypic consequences of reducing expression of a gene of interest, especially for essential genes.
Zinc Finger Targeter (ZiFiT): an engineered zinc finger/target site design tool (2007)

Zinc Finger Targeter (ZiFiT) is a simple and intuitive web-based tool that facilitates the design of zinc finger proteins (ZFPs) that can bind to specific DNA sequences. The current version of ZiFiT is based on a widely employed method of ZFP design, the 'modular assembly' approach, in which pre-existing individual zinc fingers are linked together to recognize desired target DNA sequences. Several research groups have described experimentally characterized zinc finger modules that bind many of the 64 possible DNA triplets. ZiFiT leverages the combined capabilities of three of the largest and best characterized module archives by enabling users to select fingers from any of these sets. ZiFiT searches a query DNA sequence for target sites for which a ZFP can be designed using modules available in one or more of the three archives. In addition, ZiFiT output facilitates identification of specific zinc finger modules that are publicly available from the Zinc Finger Consortium. ZiFiT is freely available at http://bindr.gdcb.iastate.edu/ZiFiT/.
Protease Inhibitors Suppress Fibrinolytic Activity of Herpesvirus-transformed Cells (1982)

Previous studies in this laboratory have quantified the fibrinolytic activity of herpesvirus-transformed cell lines and implicated the proteolytic capacity of cloned cell lines in the formation of primary and metastatic tumours. Because of the involvement of proteases in tumourigenesis in this system, we examined the effect of various protease inhibitors (alpha-1-antitrypsin, leupeptin and alpha-2-macroglobulin), as well as hamster serum containing acute phase proteins generated in response to physiological trauma, on the fibrinolytic capacity of a herpes simplex virus type 2-transformed hamster cell line. The effects of the various inhibitors on cell growth, fibrinolysis in vitro and tumourigenesis were examined. Leupeptin, alpha-1-antitrypsin, alpha-2-macroglobulin and hamster serum containing acute phase proteins were capable of inhibiting fibrinolysis in vitro, were not toxic to the cells and their action was reversible, while rejection of a mixture of protease inhibitor and transformed cells resulted in delayed tumour development.
Akt activation increases cellular cholesterol by promoting the proteasomal degradation of Niemann–Pick C1 (2015)

Null mutations of the Niemann-Pick type C1 (NPC1) gene cause NPC disease, a lysosomal storage disorder characterized by cholesterol accumulation in late endosomes (LE) and lysosomes (Ly). Nascent or mutated NPC1 is degraded through the ubiquitin-proteasome pathway, but how NPC1 degradation is regulated remains currently unknown. In the present study, we demonstrated a link between NPC1 degradation and the Akt (protein kinase B)/mTOR [mammalian (or mechanistic) target of rapamycin] signalling pathway in cervical cancer cell lines. We provided evidence that activated Akt/mTOR pathway increased NPC1 degradation by ∼50% in C33A cells when compared with SiHa or HeLa cells. NPC1 degradation in C33A cells was reversed when Akt/mTOR activation was blocked by specific inhibitors or when mTORC1 (mTOR complex 1) was disrupted by regulatory associated protein of mTOR (Raptor) knockdown. Importantly, inhibition of the Akt/mTOR pathway led to decreased NPC1 ubiquitination in C33A cells, pointing to a role of Akt/mTOR in the proteasomal degradation of NPC1. Moreover, we found that NPC1 depletion in several cancer cell lines inhibited cell proliferation and migration. Our results uncover Akt as a key regulator of NPC1 degradation and link NPC1 to cancer cell proliferation and migration.
Identification of a functional domain of human granulocyte colony-stimulating factor using neutralizing monoclonal antibodies. (1991)

Human granulocyte colony-stimulating factor (G-CSF) is a hemopoietic growth factor that is being used successfully to treat various forms of neutropenia. To define functionally important regions of G-CSF, we have prepared 37 monoclonal anti-G-CSF antibodies and mapped the regions of G-CSF recognized by different antibody groups. Antibodies recognizing similar epitopes were identified by competition assays, neutralization assays, conformation dependence and cross-reactivity with canine G-CSF. Seven of eight neutralizing antibodies fell into two related epitope groups and were conformation-dependent. The eighth was unrelated and conformation-independent. Peptides of G-CSF were generated by chemical or enzymatic digestion and tested for antibody reactivity. One of the neutralizing antibodies (LMM351) recognized a small, disulfide-bonded peptide from the V8 protease digest (residues 34-46). A synthetic peptide (residues 20-58) was recognized by all the neutralizing antibodies, implicating this disulfide-bonded loop in receptor binding. The epitopes recognized by nonneutralizing antibodies were found throughout G-CSF. Thus, regions of G-CSF that are not involved in receptor binding have also been defined. A CNBr peptide (residues 1-121) had greatly reduced biological activity, indicating that the COOH terminus is required for receptor binding. We predict that residues 20-46 and the COOH terminus bind to the G-CSF receptor.
Effect of Point Mutations on the Kinetics and the Inhibition of Human Immunodeficiency Virus Type 1 Protease: Relationship to Drug Resistance (1995)

Mutations of human immunodeficiency virus type 1 (HIV-1) protease at four positions, Val82, Asp30, Gly48, and Lys45 were analyzed for the resulting effects on kinetics and inhibition. In these mutants, Val82 was substituted separately by Asn, Glu, Ala, Ser, Asp, and Gln; Asp30 was individually substituted by Phe or Trp; Gly48 by His, Asp, and Tyr, respectively; and Lys45 by Glu. By examination of the inhibition of a single inhibitor, the differences in Ki values between the native and mutant enzymes can range from very large to insignificant even for the mutants with substitutions at the same position. By examination of a single mutant enzyme, the same broad range of Ki changes was observed for a group of inhibitors: Thus, how much the inhibition changes from the wild-type enzyme to a mutant is dependent on both the mutation and the inhibitor. The examination of Ki changes of inhibitors with closely related structures binding to Val82 mutants also reveals that the change of inhibition involves subsites in which Val82 is not in direct contact, indicating a considerable flexibility of the conformation of HIV protease. For the catalytic activities of the mutants, the kcat and Km values of many Val82 mutants and a Lys45 mutant are comparable to the native enzyme. Surprisingly, Gly48 mutations produce enzymes with catalytic efficiency superior to that of the wild-type enzyme by as much as 10-fold. Modeling of the structure of the mutants suggests that the high catalytic efficiency of some substrates is related to an increase of rigidity of the flap region of the mutants. The examination of the relative changes of inhibition and catalysis of mutants suggests that some of the Val82 and Gly48 mutants are potential resistance mutants. However, the resistance is specific with respect to individual inhibitors.
A PDTB-styled end-to-end discourse parser (2012)

Abstract Since the release of the large discourse-level annotation of the Penn Discourse Treebank (PDTB), research work has been carried out on certain subtasks of this annotation, such as disambiguating discourse connectives and classifying Explicit or Implicit relations. We see a need to construct a full parser on top of these subtasks and propose a way to evaluate the parser. In this work, we have designed and developed an end-to-end discourse parser-to-parse free texts in the PDTB style in a fully data-driven approach. The parser consists of multiple components joined in a sequential pipeline architecture, which includes a connective classifier, argument labeler, explicit classifier, non-explicit classifier, and attribution span labeler. Our trained parser first identifies all discourse and non-discourse relations, locates and labels their arguments, and then classifies the sense of the relation between each pair of arguments. For the identified relations, the parser also determines the attribution spans, if any, associated with them. We introduce novel approaches to locate and label arguments, and to identify attribution spans. We also significantly improve on the current state-of-the-art connective classifier. We propose and present a comprehensive evaluation from both component-wise and error-cascading perspectives, in which we illustrate how each component performs in isolation, as well as how the pipeline performs with errors propagated forward. The parser gives an overall system F 1 score of 46.80 percent for partial matching utilizing gold standard parses, and 38.18 percent with full automation.
Expression of hypoxia-inducible factor 1: mechanisms and consequences (2000)

Hypoxia-inducible factor 1 (HIF-1) is a basic-helix-loop-helix transcription factor that plays essential roles in mammalian development and physiology. HIF-1 is a heterodimer composed of HIF-1alpha and HIF-1beta subunits. The expression and activity of the HIF-1alpha subunit are tightly regulated by cellular O2 concentration. Under hypoxic conditions, HIF-1 activates the transcription of genes encoding erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other genes whose protein products increase O2 delivery or facilitate metabolic adaptation to hypoxia. HIF-1 is essential for embryonic vascularization and survival, neovascularization in ischemic myocardium, hypoxia-induced pulmonary vascular remodeling, and tumor vascularization. HIF-1alpha is overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. Pharmacologic manipulation of HIF-1 levels may provide a novel therapeutic approach to diseases that represent the most common causes of mortality in Western society, including cancer, chronic lung disease, and myocardial ischemia.
FPGA-based template matching using distance transforms (2003)

This paper presents a high-performance FPGA solution to generic shape-based object detection in images. The underlying detection method involves representing the target object by binary templates containing positional and directional edge information. A particular scene image is preprocessed by edge segmentation, edge cleaning and distance transforms. Matching involves correlating the templates with the distance-transformed scene image and determining the locations where the mismatch is below a certain user-defined threshold. Although successful in the past, a significant drawback of these matching methods has been their large computational cost when implemented on a sequential general-purpose processor. In this paper we present a step by step implementation of the components of such object detection systems, taking advantage of the data and logical parallelism opportunities offered by an FPGA architecture. The realization of a pipelined calculation of the preprocessing and correlation on FPGA is presented in detail.
Altered expression level of Sigma1 receptor gene in human colorectal cancer (2013)

Nonopioid Sigma1 receptor (Sig1R) influences numerous metabolism functions including regulation of ion channels, reaction on stress and response to growth signals. Due to this influence, Sigma1 receptor ligands show anti-proliferative and cytotoxic action on tumor cells. Additionally its increased level is observed in some types of tumors. Colorectal cancer is one of the most common cancers worldwide and its clinical development is well described. The aim of the study was evaluation of Sigma1 receptor mRNA expression level in human colorectal cancer and colorectal cancer liver metastases at different stages of tumor development. The mRNA was isolated from 30 patients: 18 with colorectal cancer (CRC) and 12 with colorectal cancer liver metastases (CRCLM). The cDNA of Sig1R gene was amplified by polymerase chain reaction using specific primers. The level of Sig1R mRNA expression was determined by measurement of optical density. Sig1R expression level was increased in CRC and CRCLM. The highest level of Sig1R mRNA was observed in UICC stage III. We also showed significant interactions of UICC stage and tumor localization with Sig1R expression level. There were no interactions between UICC stage and age of patients, although we observed significantly decreased level of Sig1R mRNA in older patients. Clinical advancement stage, localization of tumor and age of patients seems to be an important factors influencing Sigma1 receptor expression level. It is probably due to double nature of Sig1R action - in certain conditions it could act pro- or antiapoptotic. This action might depend on Sig1R activity resulting from its expression level.
Synthesis of C-D-ring analogues of the azasteroid A25822 (1996)

A. J. Sutherland, J. K. Sutherland and P. J. Crowley, J. Chem. Soc., Perkin Trans. 1, 1996, 349 DOI: 10.1039/P19960000349
Comments on "An architecture for addition and subtraction of long word length numbers in the logarithmic number system" by D.M. Lewis (1992)

D.M. Lewis (ibid., vol.39, no.11, p.1325-36, Nov. 1990) recently described an architecture for performing addition and subtraction in the logarithmic number system using a Taylor series approximation and ROM tables. Here it is shown that a 25% improvement can be achieved in the table used to implement addition. This improvement is significant when Lewis' technique is used to implement variations of the logarithmic number system which do not require the subtraction logarithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Enzymatic identification of the load-bearing boundary lubricant in the joint. (1998)

Bovine articular cartilage and synovial fluid (SF) were co-incubated with one of three enzymes selected to destroy each of the three major contenders for the active ingredient imparting such remarkable load-bearing lubrication to the normal joint. Destroying hyaluronic acid (HA), alias hyaluronan, with hyaluronidase, both frictional and wear tests displayed no significant change in accordance with most previous studies of SF alone. Destroying surface-active phospholipid (SAPL) with phospholipase A2, there was a highly significant dose-dependent compromise of lubrication as recorded on both tests. Trypsin produced a somewhat surprising result in that lubrication of the cartilage actually improved. This result can be interpreted as indicating that lubricin is not the lubricant per se, but, as a water-soluble, macromolecular, proteinaceous carrier for phospholipid, its destruction caused more SAPL to be deposited as the true load-bearing lubricant. These results are discussed in the context that SAPL, lubricin and HA each have specific roles in a comprehensive lubrication system.
Designed Synthesis of 3D Covalent Organic Frameworks (2007)

Three-dimensional covalent organic frameworks (3D COFs) were synthesized by targeting two nets based on triangular and tetrahedral nodes: ctn and bor. The respective 3D COFs were synthesized as crystalline solids by condensation reactions of tetrahedral tetra(4-dihydroxyborylphenyl) methane or tetra(4-dihydroxyborylphenyl)silane and by co-condensation of triangular 2,3,6,7,10,11-hexahydroxytriphenylene. Because these materials are entirely constructed from strong covalent bonds (C-C, C-O, C-B, and B-O), they have high thermal stabilities (400 degrees to 500 degrees C), and they also have high surface areas (3472 and 4210 square meters per gram for COF-102 and COF-103, respectively) and extremely low densities (0.17 grams per cubic centimeter).
Intracellular Distribution and Some Properties ofβ-Glucosidases of a Cellulolytic Pseudomonad (1976)

Journal Article Intracellular Distribution and Some Properties of β-Glucosidases of a Cellulolytic Pseudomonad Get access Jun-Ton Hwang, Jun-Ton Hwang Department of Botany, Faculty of Science, Tokyo Kyoiku University, Otsuka, Tokyo Present address: Department of Chemistry, Chung Yuan Christian College of Science and Engineering, Chung Li, Taiwan, China. Search for other works by this author on: Oxford Academic Google Scholar Hiroshi Suzuki Hiroshi Suzuki Department of Botany, Faculty of Science, Tokyo Kyoiku University, Otsuka, Tokyo Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 40, Issue 11, 1 November 1976, Pages 2169–2175, https://doi.org/10.1080/00021369.1976.10862376 Published: 01 November 1976 Article history Received: 17 May 1976 Published: 01 November 1976
A Structural Signature Characteristic of the Calycin Protein Superfamily (1995)

Abstract: A triumvirate of protein families (the lipocalins, fatty acid-binding proteins, and avidins) together form a structural superfamily: the calycins. A similar pattern of specific side chain contacts between conserved residues is shown to be characteristic of all three calycin member families. An arginine or lysine (from the last strand of the β-barrel), forms several potential hydrogen bonds with the main chain carbonyls of a short N-terminal 3 10 ­- like helix and packs across a conserved tryptophan (from the first strand of the β-barrel).