gebhart/patrepeval huggingface dataset:
Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression (2000)

Vascular endothelial growth factor (VEGF) is an important factor mediating tumour angiogenesis. VEGF mRNA is differentially expressed in bladder cancer with high expression in superficial tumours (stage pTa and pT1) contrasting with low expression in muscle invasive tumours (stage > or = pT2). To investigate mechanisms regulating VEGF expression in bladder cancer, VEGF mRNA and protein were measured in normal bladder (n = 12) and primary bladder cancers (n = 57). VEGF protein levels correlated with mRNA expression in normal bladder (r = 0.68, P = 0.02) and bladder cancer (r = 0.46, P = 0.0007). Whilst VEGF mRNA expression was threefold higher in superficial compared to muscle invasive bladder cancers (P = 0.0001) there was no difference in VEGF protein (P = 0.81). Accordingly, the median protein:mRNA ratios increased more than 15-fold with increasing tumour stage (P < 0.0001) suggesting translational regulation. Expression of the eukaryotic initiation factor-4E (elF-4E), a factor implicated in the translational regulation of VEGF, was greater in tumours than normal bladder (P < 0.0001) and correlated with VEGE protein:mRNA ratios (n = 43, r = 0.54, P = 0.0004) pointing to its role in the regulation of VEGF. In superficial tumours (n = 37) high expression of eIF-4E was associated with a poor prognosis and reduced stage progression-free survival (P = 0.04, Cox proportional hazards model). The study demonstrates that eIF-4E may be involved in translational regulation of VEGF in bladder cancer and might have a role as a prognostic factor in bladder cancer.
MicroRNA epigenetic alterations: predicting biomarkers and therapeutic targets in human diseases (2008)

MicroRNAs (miRNAs) consist of a class of evolutionarily conserved small non-coding RNA that regulates target messenger RNAs by mechanisms such as incomplete base pairing and post-transcriptional gene silencing. Recent studies have shown that aberrant miRNA expression is a common feature of many human disorders including aging, heart diseases, cancer, autoimmune diseases and others. It seems likely that miRNA expression levels can be used as novel diagnostic markers. MiRNAs may also provide a new strategy for therapeutic interventions. In this review, we focus on recent advances in understanding how miRNA changes contribute to disease development and their potential as novel biomarkers and therapeutic targets for human diseases.
Support logic programming (1986)

This article describes a support logic programming system which uses a theory of support pairs to model various forms of uncertainty. It should find application to designing expert systems and is of a query language type like Prolog. Uncertainty associated with facts and rules is represented by a pair of supports and uses ideas from Zadeh's fuzzy set theory and Shafer's evidence theory. A calculus is derived for such a system and various models of interpretation given. the article provides a form of knowledge representation and inference under uncertainty suitable for expert systems and a closed world assumption is not assumed. Facts not in the knowledge base are uncertain rather than assumed to be false.
Optimization of repetition spacing in the practice of learning (1994)

A universal formula for computing inter-repetition intervals in paired-associate learning has been determined for the knowledge retention level of 95%. It is claimed that the formula could be used in the practice of learning for a wide range of subjects, regardless individual learner's capacity.
Diastereoselective Encapsulation of Tartaric Acid by a Helical Aromatic Oligoamide (2010)

A helical aromatic oligoamide foldamer encapsulates tartaric acid with exceptional affinity, selectivity, and diastereoselectivity. The structure of the complex has been elucidated both in solution by NMR spectroscopy and in the solid state by X-ray crystallography, making it possible to rationalize the strong effects observed, particularly the role of hydrogen bonds between the hydroxyl and carboxylic acid groups of tartaric acid and the inner wall of the helically folded capsule, which completely surrounds the guest and insulates it from the solvent.
Underground/Submarine Cable Protection Using a Negative-Sequence Directional Comparison Scheme (2000)

Protective relaying requirements for underground and submarine cables are different from those for overhead lines. This paper analyzes the application of directional comparison schemes to protect two 34.5 kV submarine cables. These cables are 24-km long and connect Cozumel Island to Mexico’s mainland network. The paper discusses cable modeling using symmetrical components and analyzes the performance of a negative-sequence directional element during cable fault conditions. INTRODUCTION Traditionally, current-differential relays have protected cables in transmission and distribution applications. These applications also require directional overcurrent or distance relays to provide protection when the communications channel is out-of-service. This paper proposes an alternative solution for unbalanced fault protection. The solution is based on negative-sequence directional relays in a directional comparison scheme. This solution provides excellent fault resistance coverage and does not require additional backup protection. The paper also analyzes the performance of the directional relay in cable applications when the cable admittance is not negligible. UNDERGROUND AND SUBMARINE CABLE PROTECTION Power cables are the most reliable means of connecting different equipment in an electric system [1]. They can be used as transmission or distribution links. We expect more power cable applications in electric systems because of advances in cross-linked polyethylene (XLPE) cable technology, environmental restrictions, and right-of-way availability. Power cables require protection for overload and short-circuit current conditions. Power cable protection applications must consider different cable impedance characteristics and configurations.
10-valent pneumococcal nontypeableHaemophilus influenzaePD conjugate vaccine: Synflorix™ (2009)

The global burden of disease due to Streptococcus pneumoniae remains high. The licensed 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar) has successfully reduced invasive disease in the USA, but serotype coverage is incomplete and some evidence suggests that serotype replacement has occurred. Recently, a new 10-valent pneumococcal nontypeable Haemophilus influenzae (NTHi) protein D (PD) conjugate vaccine (PHiD-CV, Synflorix) has been licensed in more than 40 countries, including Europe, for the prevention of invasive disease and acute otitis media (AOM) due to pneumococcus in infants and children. PHiD-CV is immunogenic in infants when administered as a three-dose primary vaccination in a range of schedules and has a safety profile comparable to that of 7vCRM. Additional serotypes in PHiD-CV (1, 5 and 7F) increase overall serotype coverage and improve coverage in specific age groups and against specific disease syndromes. The use of the PD carrier, which provided protection against AOM caused by NTHi in a large efficacy trial testing a prototype of the final vaccine formulation, suggests that PHiD-CV will also provide some protection against AOM due to NTHi.
Myelodysplastic/Myeloproliferative Neoplasms (2011)

According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, myelodysplastic/myeloproliferative neoplasms are clonal myeloid neoplasms that have some clinical, laboratory, or morphologic findings that support a diagnosis of myelodysplastic syndrome, and other findings that are more consistent with myeloproliferative neoplasms. These disorders include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia (BCR-ABL1 negative), juvenile myelomonocytic leukemia, and myelodysplastic/myeloproliferative neoplasms, unclassifiable. The best characterized of these latter unclassifiable conditions is the provisional entity defined as refractory anemia with ring sideroblasts associated with marked thrombocytosis. This article focuses on myelodysplastic/myeloproliferative neoplasms of adulthood, with particular emphasis on chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts associated with marked thrombocytosis. Recent studies have partly clarified the molecular basis of these disorders, laying the groundwork for the development of molecular diagnostic and prognostic tools. It is hoped that these advances will soon translate into improved therapeutic approaches.
Cytotoxic lymphocyte maturation factor (interleukin 12) is a synergistic growth factor for hematopoietic stem cells. (1993)

The recently cloned cytotoxic lymphocyte maturation factor (interleukin 12 [IL-12]) has been described as a growth factor for mature lymphocytes. The present study investigated whether purified recombinant murine IL-12 (rMuIL-12) also could affect the proliferation of primitive bone marrow progenitor cells. Using a population of Lin-Sca-1+ murine bone marrow stem cells, we now demonstrate that IL-12 is a potent synergistic factor for primitive hematopoietic stem cells. The synergy of IL-12 was observed in single-cell cloning assays, demonstrating that its effects are directly mediated. Specifically, IL-12 enhanced stem cell factor-induced myelopoiesis of Lin-Sca-1+ cells sevenfold, and synergized with colony-stimulating factors (CSFs) to induce proliferation of Lin-Sca-1+ stem cells. IL-12 increased the number of responding progenitor cells as well as the size of the colonies formed. IL-12 also increased colony formation of high proliferative potential colony-forming cells with multiple CSF combinations. The effects of IL-12 were concentration dependent with a 50% effective dose of 2-20 and 20-200 ng/ml, resulting in maximum stimulation. Furthermore, a neutralizing anti-IL-12 antibody blocked the synergistic effects of rMuIL-12. In addition, IL-12 was found to have synergistic effects on more committed bone marrow progenitors as well. Our results therefore suggest that in addition to being a potent lymphopoietic stimulator, IL-12 is a regulator of the growth of hematopoietic stem cells and their myeloid progeny.
Graft-versus-Host Disease after Double-Unit Cord Blood Transplantation Has Unique Features and an Association with Engrafting Unit-to-Recipient HLA Match (2013)

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.
Involvement of Granulocyte-Macrophage Colony-Stimulating Factor in Pulmonary Homeostasis (1994)

The in vivo function of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) was investigated in mice, carrying a null allele of the GM-CSF gene, that were generated by gene targeting techniques in embryonic stem cells. Although steady-state hematopoiesis was unimpaired in homozygous mutant animals, all animals developed the progressive accumulation of surfactant lipids and proteins in the alveolar space, the defining characteristic of the idiopathic human disorder pulmonary alveolar proteinosis. Extensive lymphoid hyperplasia associated with lung airways and blood vessels was also found, yet no infectious agents could be detected. These results demonstrate that GM-CSF is not an essential growth factor for basal hematopoiesis and reveal an unexpected, critical role for GM-CSF in pulmonary homeostasis.
Purification, characterization, and comparison of the immunoglobulin A1 proteases of Neisseria gonorrhoeae (1988)

Each isolate of Neisseria gonorrhoeae produces one of two distinct immunoglobulin A1 (IgA1) proteases, type 1 or type 2, which are known to possess different cleavage specificities for peptide bonds in the hinge region of human IgA1. Both proteases were secreted into the culture medium throughout exponential growth; however, the activity level of the type 2 protease was 10-fold that observed for the type 1 enzyme. The type 2 protease was quite stable and resistant to a variety of inhibitors. In contrast, the type 1 enzyme was highly unstable and inhibited by low concentrations of metal chelators, salts, and thiol- or serine-specific chemical reagents. Both types of gonococcal IgA1 protease were purified from broth culture supernatants by a combination of anion-exchange, chromatofocusing, and molecular sieve chromatography techniques. The stable type 2 enzyme comprised a 114-kilodalton (kDa) peptide which converted to a still active 109-kDa peptide during isolation. In contrast, the type 1 protease possessed a 112-kDa peptide which did not convert to a smaller form and which could not be dissociated from peptides of 34 and 31 kDa without complete loss of enzyme activity.
Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF‐1–CXCR4 Axis (2005)

The alpha-chemokine stromal-derived factor (SDF)-1 and the G-protein-coupled seven-span transmembrane receptor CXCR4 axis regulates the trafficking of various cell types. In this review, we present the concept that the SDF-1-CXCR4 axis is a master regulator of trafficking of both normal and cancer stem cells. Supporting this is growing evidence that SDF-1 plays a pivotal role in the regulation of trafficking of normal hematopoietic stem cells (HSCs) and their homing/retention in bone marrow. Moreover, functional CXCR4 is also expressed on nonhematopoietic tissue-committed stem/progenitor cells (TCSCs); hence, the SDF-1-CXCR4 axis emerges as a pivotal regulator of trafficking of various types of stem cells in the body. Furthermore, because most if not all malignancies originate in the stem/progenitor cell compartment, cancer stem cells also express CXCR4 on their surface and, as a result, the SDF-1-CXCR4 axis is also involved in directing their trafficking/metastasis to organs that highly express SDF-1 (e.g., lymph nodes, lungs, liver, and bones). Hence, we postulate that the metastasis of cancer stem cells and trafficking of normal stem cells involve similar mechanisms, and we discuss here the common molecular mechanisms involved in these processes. Finally, the responsiveness of CXCR4+ normal and malignant stem cells to an SDF-1 gradient may be regulated positively/primed by several small molecules related to inflammation which enhance incorporation of CXCR4 into membrane lipid rafts, or may be inhibited/blocked by small CXCR4 antagonist peptides. Consequently, strategies aimed at modulating the SDF-1-CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells.
Dual Delivery of Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Coacervate Displays Strong Angiogenic Effects (2014)

Controlled delivery of multiple growth factors (GFs) holds great potential for the clinical treatment of ischemic diseases and might be more therapeutically effective to reestablish vasculature than the provision of a single GF. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are two potent angiogenic factors. However, due to rapid degradation and dilution in the body, their clinical potential will rely on an effective mode of delivery. A coacervate, composed of heparin and a biodegradable polycation, which protects GFs from proteolysis and potentiates their bioactivities, is developed. Here, the coacervate incorporates VEGF and HGF and sustains their release for at least three weeks. Their strong angiogenic effects on endothelial cell proliferation and tube formation in vitro are confirmed. Furthermore, it is demonstrated that coacervate-based delivery of these factors has stronger effects than free application of both factors and to coacervate delivery of each GF separately.
Functional selection and characterization of DNA binding sites for trp repressor of Escherichia coli. (1994)

trp repressor of Escherichia coli controls transcription initiation in operons involved in tryptophan biosynthesis by binding to operator sequences within the regulated promoters. Naturally occurring operators are homologous over an 18-base pair region and display dyad symmetry. We have examined the sequence determinants of a repressor binding site using a functional selection/polymerase chain reaction (PCR) amplification strategy. A trp repressor affinity column was generated and used to select binding-competent DNAs from a randomized pool of synthetic double-stranded DNA. DNAs that showed tryptophan-dependent high-affinity binding were eluted by addition of the tryptophan analog beta-indole acrylic acid and amplified by PCR. Following iterative cycles of affinity chromatography and PCR, the selected DNAs were cloned and sequenced. The CTAG tetranucleotide, present in the consensus sequence of all natural operators, was found in all selected DNAs. Mapping experiments utilizing the repressor affinity column showed the CTAG motif to be a critical determinant for repressor binding. Quantitative electrophoretic mobility shift assays with purified trp repressor revealed that although some of the DNAs were bound by one repressor dimer, others were bound by two repressor dimers with cooperativity. Measured binding constants ranged from 0.035 to 0.5 nM for the selected DNAs, compared with 0.1 nM for the trp operator.
Effects of streptonigrin derivatives and sakyomicin A on the respiration of isolated rat liver mitochondria. (1986)

Though all the streptonigrin derivatives with modifications in the carboxyl group on C2' were active as electron acceptors in the oxidation of NADH by Clostridium kluyveri diaphorase as well as streptonigrin, the glycine derivative did not show any marked effect on the KCN-insensitive oxidation of glutamate by rat liver mitochondria, suggesting a poor membrane transport of the glycine derivative. Sakyomicin A also induced the KCN-insensitive oxidation of glutamate by mitochondria, while a trace activity was observed by mitomycin C and the effect of doxorubicin was negligible. Like streptonigrin, the autoxidation of a reduced form (hydroquinone) of sakyomicin A to a quinone accompanied the generation of H2O2. However, exogenous NADH was oxidized by mitochondria in the presence of sakyomicin A but not streptonigrin.
Ultrashort Microwave-Induced Thermoacoustic Imaging: A Breakthrough in Excitation Efficiency and Spatial Resolution (2012)

With theoretical prediction and experimental validation, we propose a novel approach to significantly enhance the conversion efficiency of thermoacoustic (TA) imaging by using an ultrashort microwave pulse. The implementation of the ultrashort microwave pulse leads to orders of magnitude enhancement in excitation efficiency and spatial resolution, compared to that from existing TA imaging techniques. This allows high-resolution (~ 100 micron resolution) TA imaging to be acquired noninvasively. The present work represents a major breakthrough in the conversion efficiency of the TA effect and the resolution of TA imaging, which can potentially be used for clinical imaging.
Sequential changes in trace metal, metallothionein and calmodulin concentrations in healing skin wounds (1999)

Metalloenzymes have an important role in repair and regenerative processes in skin wounds. Demands for different enzymes vary according to the phase in the healing cascade and constituent events. Sequential changes in the concentrations of calcium, copper, magnesium and zinc were studied in the incisional wound model in the rat over a 10 d period. Copper levels remained low (< 10 microg/g dry weight) throughout, but calcium, magnesium and zinc increased from wounding and peaked at about 5 d at a time of high inflammation, granulation tissue formation and epidermal cell proliferation. Metal concentrations declined to normal by 7 d when inflammation had regressed, re-epithelialisation of the wound site was complete and the 'normalisation' phase had commenced. Although the wound was overtly healed by 10 d, the epidermis was still moderately hyperplastic. In view of competitive binding of trace metals at membrane receptors and carrier proteins, the ratios or balance between these trace metals was examined and the significance is discussed. Using immunocytochemistry, we demonstrated increases in metallothionein immunoreactivity as an indication of zinc and copper activity in the papillary dermis and in basal epidermal cells near the wound margin 1-5 d after wounding. This is consistent with metalloenzyme requirements in inflammation and fibrogenesis. Calmodulin, a major cytosolic calcium binding protein was highest in maturing keratinocytes and in sebaceous gland cells of normal skin; it was notably more abundant in the epidermis near the wound margin and in re-epithelialising areas at a time when local calcium levels were highest.
FULL-VECTORIAL PARALLEL FINITE-ELEMENT CONTRAST SOURCE INVERSION METHOD (2013)

The multiplicatively regularized finite-element contrast source inversion algorithm (MR-FEM-CSI) is used to solve the fullvectorial three-dimensional (3D) inverse scattering problem. The contrast and contrast-source optimization variables are located at the centroids of tetrahedra within the problem domain; whereas the electric field is expanded in terms of edge basis functions on the same tetrahedra. A dual-mesh is created in order to apply the multiplicative regularization. To handle large-scale problems the inversion algorithm is parallelized using the MPI library, with sparse matrix and vector computations supported by PETSc. The algorithm is tested using experimental datasets obtained from the Institut Fresnel database. A synthetic example shows that the technique is able to successfully image moisture hot-spots within a partially filled grain bin.