gebhart/patrepeval huggingface dataset:
Fast best-effort pattern matching in large attributed graphs (2007)

We focus on large graphs where nodes have attributes, such as a social network where the nodes are labelled with each person's job title. In such a setting, we want to find subgraphs that match a user query pattern. For example, a "star" query would be, "find a CEO who has strong interactions with a Manager, a Lawyer,and an Accountant, or another structure as close to that as possible". Similarly, a "loop" query could help spot a money laundering ring.
Studies of recombinant plasminogen activator inhibitor-1 in rabbits. Pharmacokinetics and evidence for reactivation of latent plasminogen activator inhibitor-1 in vivo. (1990)

The pharmacokinetics of human recombinant plasminogen activator inhibitor-1 (rPAI-1) was studied in rabbits. Latent rPAI-1 (0-2 units of tissue-type plasminogen activator neutralizing activity per microgram protein); reactivated rPAI-1 (approximately 150 units/micrograms); and chloramine T-oxidized, nonreactivatable rPAI-1 (approximately 0.7 units/microgram) were studied. The pharmacokinetic parameters for the disposition of rPAI-1 antigen after an intravenous bolus injection of 1.0 or 2.5 mg/kg rPAI-1 were very similar for all three forms: the initial volume of distribution was approximately 60 ml/kg, the initial half-life in plasma was 6 minutes, and the plasma clearance was approximately 4 ml/kg/min. The disposition of PAI activity after injection of reactivated rPAI-1 was similar to that of rPAI-1 antigen. Injection of latent rPAI-1 was associated with a nearly threefold increase in the specific activity of circulating PAI-1 from 2 units/micrograms to 5.0 +/- 1.1 units/micrograms (p less than 0.01) within 1 minute, followed by a cumulative 25-fold increase in specific activity over 1 hour (p = 0.01). In contrast, the specific activity of oxidized or reactivated preparations of rPAI-1 did not increase in the first several minutes after injection. These findings support the existence of a fast-acting but low-capacity mechanism for the reactivation of rPAI-1 in vivo.
Analysis of a new hepatitis C virus type and its phylogenetic relationship to existing variants (1992)

Sequences obtained in the 5' non-coding region (5'NCR) of hepatitis C virus (HCV) were obtained from Scottish blood donors and compared with previously published HCV sequences. Phylogenetic analysis revealed the existence of three distinct groups of sequences; two of these corresponded to the recently described HCV types 1 and 2 variants, while viral sequences detected in around a third of the blood donors formed a separate phylogenetic group that probably represents infection with a novel virus species. Nucleotide sequences of this latter group differed from all previously published 5'NCR sequence variants by at least 9%. This new virus type also differed considerably from previously published variants in other regions of the viral genome (core, NS-3 and NS-5), with corrected nucleotide distances of 15, 43 and 49% respectively from the prototype HCV-1 sequence. Formal phylogenetic analysis of each of the coding regions confirmed that HCV type 1 variants could be clearly differentiated into regional variants (Far East and U.S.A./European), in contrast to the clearly overlapping geographical distributions of the main HCV types in U.K. blood donors. We discuss the evidence for and against the hypothesis that the three main phylogenetic groups identified in this study represent separate species of HCV.
Enabling tetracationic cyclophane production by trading templates (2010)

The time taken to produce the ubiquitous and promiscuous receptor, which has become known as the little “blue box”, has been halved as a result of using a pH-responsive derivative of 1,5-diaminonaphthalene to displace the template employed during its synthesis. The fact that this surrogate trades places within the cavity of the “blue box” is the key to the time-saving for the simple reason that it leaves the lock, so-to-speak, as soon as it becomes protonated by a strong acid. During the subsequent full characterisation of the “blue box”, it was discovered that the tetracationic cyclophane exists at least in two different polymorphs in the solid state.
siRNA therapy for cancer and non-lethal diseases such as arthritis and osteoporosis (2010)

Most musculoskeletal disorders, such as rheumatoid arthritis, osteoarthritis, fracture, aseptic loosening, cartilage and intervertebral disc degeneration are non-fatal and age-related chronic inflammatory conditions, but represent significant morbidity and a socio-economic burden. siRNA-based gene therapy offers treatment opportunities that are less invasive, more effective and less expensive than existing modalities. Future directions for siRNA therapy include the development of safe and more efficient delivery systems and the selection of optimal gene targets for disease control.
Autoimmune Haemolysis Associated with Donath-Landsteiner Antibodies (1982)

The clinical pattern of haemolysis associated with Donath-Landsteiner antibodies has undergone a change over the years. In the current study 13 patients developed the acute form of the disease whilst only 1 presented with the classical picture of chronic paroxysmal cold haemoglobinuria. The acute illness typically occurred in young children with a male predominance of about 2.5:1; 10 patients were less than 5 years old. There was often a history of a preceding infection, the onset was sudden, prostration, haemoglobinuria and pallor were prominent. The patients were very ill but rapid and complete recovery usually occurred within a few days; however, 1 patient died. Treatment consisted of rest and warmth; in addition blood transfusion was needed in 7 patients. The chronic disease (which was non-syphilitic in origin) followed a benign course, warmth and avoidance of cold being all that were necessary to maintain the patient's well-being. It is felt that the general term for this disorder should be Donath-Landsteiner haemolysis rather than the traditional paroxysmal cold haemoglobinuria.
Hydrodynamics of an Undulating Fin for a Wave-Like Locomotion System Design (2011)

Motivated by the interest to develop an agile, high-efficiency robotic fish for underwater applications where safe environment for data-acquisition without disturbing the surrounding during exploration is of particular concern, this paper presents computational and experimental results of a biologically inspired mechanical undulating fin. The findings offer intuitive insights for optimizing the design of a fin-based robotic fish that offers several advantages including low underwater acoustic noise, dexterous maneuverability, and better propulsion efficiency at low speeds. Specifically, this paper begins with the design of a robotic fish developed for experimental investigation and for validating computational hydrodynamic models of an undulating fin. A relatively complete computational model describing the hydrodynamics of an undulating fin is given for analyzing the effect of propagating wave motions on the forces acting on the fin surface. The 3-D unsteady fluid flow around the undulating fin has been numerically solved using computational fluid dynamics method. These numerically simulated pressure and velocity distributions acting on the undulating fin, which provide a basis to compute the forces acting on the undulating fin, have been experimentally validated by comparing the computed thrust against data measured on a prototype flexible-fin mechanism.
A potential role for antisense oligonucleotide analogues in the development of oncogene targeted cancer chemotherapy. (1990)

The identification of activated oncogenes as the basic biochemical difference between tumour cells and normal cells has opened up the possibility for development of truly tumour specific chemotherapy. It may be hypothesized that malignant cells would revert to a more normal phenotype and might even be triggered into terminal differentiation if expression of the appropriate oncogenes were inhibited. Although, at present, it is not possible to anticipate what form future therapy based upon this approach would take, it is clear that the immediate priority must be to establish the general validity of the hypothesis with a variety of tumour cell types in vitro. For this purpose antisense oligonucleotide analogues appear to offer considerable promise as sequence specific inhibitors of oncogene expression. However, no analogue structure yet devised fulfils all the requirements of an ideal antisense effector in terms of biological stability, cell uptake, non-toxicity, hybridization efficiency and mechanism of action on target nucleic acids. Inhibition of oncogene expression in certain cell types has been reported using antisense oligonucleotides but the technique is not universally applicable and more detailed biochemical investigations of the interactions of oligonucleotides with intact cells are required before improved structures may be developed.
Efficient programmable gene silencing by Cascade (2014)

Methods that permit controlled changes in the expression of genes are important tools for biological and medical research, and for biotechnological applications. Conventional methods are directed at individually changing each gene, its regulatory elements or its mRNA's translation rate. We demonstrate that the CRISPR-associated DNA-binding Cascade complex can be used for efficient, long-lasting and programmable gene silencing. When Cascade is targeted to a promoter sequence the transcription of the downstream gene is inhibited, resulting in dramatically reduced expression. The specificity of Cascade binding is provided by the integral crRNA component, which is easily designed to target virtually any stretch of DNA. Cascade targeted to the ORF sequence of the gene can also silence expression, albeit at lower efficiency. The system can be used to silence plasmid and chromosome targets, simultaneously target several genes and is active in different bacterial species and strains. The findings described here are an addition to the expanding range of CRISPR-based technologies and may be adapted to additional organisms and cell systems.
Partial purification of Xenopus laevis egg extract factor(s) that induce swelling in permeabilized human sperm (1991)

A combination of adsorption (protamine-agarose) and gel filtration (Sephacryl S-300) chromatography was used to enrich for factor(s) in Xenopus laevis frog egg extract that induce nuclear swelling-chromatin decondensation in permeabilized human sperm. It was determined that a 70-fold purification of the factor(s) that induce human sperm nuclear swelling has resulted from the purification scheme. The reduced, active factor(s) have a Kav of 0.12 and an approximate molecular weight of 290,000 daltons. The extract nuclear swelling activity is sensitive to temperatures of 50 degrees C and above, as well as proteolytic treatment. RNase and cycloheximide treatments of the extracts have no effect on the nuclear swelling activity. These data suggest that the egg extract factor(s) that induce nuclear swelling in permeabilized human sperm are protein(s) that are present in the unfertilized frog egg.
6. Polysaccharides of baker's yeast. Part IV. Mannan (1961)

S. Peat, W. J. Whelan and T. E. Edwards, J. Chem. Soc., 1961, 29 DOI: 10.1039/JR9610000029
Expression of the mouse goosecoid gene during mid-embryogenesis may mark mesenchymal cell lineages in the developing head, limbs and body wall (1993)

After an earlier, transient phase of expression in the developing primitive streak of 6.4- to 6.8-day mouse embryos, the homeobox gene goosecoid is now shown to be expressed in a later phase of mouse development, from 10.5 days onwards. The later, spatially restricted domains of goosecoid expression are detected in the head, limbs and ventrolateral body wall. At all sites, the domains of expression are first detected in undifferentiated tissue, and then expression persists as these tissues undergo subsequent morphogenesis. For example, goosecoid expression is noted in the first branchial arch at 10.5 days, and then expression persists as this tissue undergoes morphogenesis to form the lower jaw and the body of the tongue. Expression in tissues around the first branchial cleft persists as these undergo morphogenesis to form the base of the auditory meatus and eustachian tube. Expression in tissues around the newly formed nasal pits persists as these elongate to form the nasal chambers. Expression in the ventral epithelial lining of the otic vesicle persists as this eventually gives rise to the non-sensory epithelium of the cochlea. Expression in the proximal limb buds and ventrolateral body wall persists as these tissues undergo morphogenesis to form proximal limb structures and ventral ribs respectively. Our findings lead us to suggest that the goosecoid gene product plays a role in spatial programming within discrete embryonic fields, and possibly lineage compartments, during organogenesis stages of mouse development.
IGF-1 Regulates Migration and Angiogenesis of Human Endothelial Cells (1999)

Recent studies revealed favorable para- and/or autocrine effects of IGF-1 in the pathogenesis of diabetic complications. On the other hand, hyperglycemia is a risk factor for the development of diabetic vascular complications. In this study we examined the effects of high glucose and/or IGF-1 on cell migration and angiogenesis (tubular formation) by using human endothelial cells (EC) in vitro. First we examined cell migration by the two-chamber method. Chronic treatment with a high concentration of D-glucose strongly stimulated the cell migration, which was mimicked by PMA, a protein kinase C (PKC) agonist. The cell migration was also induced by IGF-1. The glucose-induced cell migration was blocked by PKC inhibitor, H7. IGF-1-induced cell migration was not blocked by PD98059, MAPK/ERK kinase (MEK) inhibitor or wortmannin, a phosphatidylinositol (PI) 3-kinase inhibitor. Next we examined the effects of high glucose and/or IGF-1 on the tubular formation of EC. The tubular formation was induced only when the cells were exposed to a combination of high glucose and IGF-1. The tubular formation was blocked by MEK inhibitor and PI 3-kinase inhibitor but not by PKC inhibitor. These results indicate that hyperglycemia and IGF-1, respectively, stimulate the EC migration, and tubular formation is induced by a combination of IGF-1 and hyperglycemia.
Three ENU-induced alleles of the murine quaking locus are recessive embryonic lethal mutations (1988)

Summary The quaking ( qk ) locus on mouse chromosome 17 has been defined by a single viable quaking allele. Three new alleles of quaking were selected after ENU mutagenesis by their failure to complement the quaking phenotype. The qk k2 allele was induced on wild-type chromatin and the qk kt1 and qk kt4 alleles were induced on t -chromatin. Each is a recessive embryonic lethal mutation. They fail to complement each other and are not complemented by the deletion, Tt Orl . Homozygotes and hemizygotes die at 8–9·5 days gestation, but not at a single precise time. Because the classical quaking mutation complements the lethality of these new alleles, but they fail to complement its quaking phenotype (myelination defect), we conclude that the quaking + function is required for embryonic survival as well as for myelination.
Upregulation of matrix metalloproteinases (MMPs) in breast cancer xenografts: A major induction of stromal MMP‐13 (2004)

In human breast cancer (HBC), as with many carcinoma systems, most matrix metalloproteinases (MMPs) are largely expressed by the stromal cells, whereas the tumour cells are relatively silent in MMP expression. To determine the tissue source of the most relevant MMPs, we xenografted HBC cell lines and HBC tissues into the mammary fat pad (MFP) or bone of immunocompromised mice and measured the expression of human and mouse MMP-2, -9, -11, -13, membrane-type-1 MMP (MT1-MMP), MT2-MMP and MT3-MMP by species-specific real-time quantitative RT-PCR. Our data confirm a stromal origin for most tumour-associated MMPs and indicate marked and consistent upregulation of stromal (mouse) MMP-13 and MT1-MMP in all xenografts studied, irrespective of implantation in the MFP or bone environments. In addition, we show increased expression of both human MMP-13 and human MT1-MMP by the MDA-MB-231 tumour cells grown in the MFP compared to in vitro production. MMP protein and activity data confirm the upregulation of MMP mRNA production and indicate an increase in the activated MMP-2 species as a result of tumour implantation. These data directly demonstrate tumour induction of MMP production by stromal cells in both the MFP and bone environments. These xenografts are a valuable means for examining in vivo production of MMPs and suggest that MMP-13 and MT1-MMP will be relevant targets for inhibiting breast cancer progression.
Application of a Cell-Once-Through Perfusion Strategy for Production of Recombinant Antibody from rCHO Cells in a Centritech Lab II Centrifuge System (2007)

Based upon the results of scale-down intermittent perfusion processes, a cell-once-through (COT) perfusion concept was applied to a dual bioreactor system coupled to a Centritech Lab II centrifuge for culture of recombinant Chinese hamster ovary (rCHO) cells for monoclonal antibody production. In this new culture mode, i.e., the COT perfusion process, total spent medium was transferred to the centrifuge and a fixed percentage was removed. Approximately 99% of the viable cells are transferred to another bioreactor filled with fresh medium by single operation of the Centritech Lab II centrifuge system for about 30 min. Accordingly, a significant reduction of the cell-passage frequency to the centrifuge led to minimization of cell damage caused by mechanical shear stress, oxygen limitation, nutrient limitation, and low temperature outside the bioreactor. The effects of culture temperature shift and fortified medium on cell growth and recombinant antibody production in the COT perfusion process were investigated. Although the suppressive effects of low culture temperature on cell growth led to a loss of stability in a long-term COT perfusion culture system, the average antibody concentration at 33 degrees C was 157.8 mg/L, approximately 2.4-fold higher than that at 37 degrees C. By the use of a fortified medium at 37 degrees C, rCHO cells were maintained at high density above 1.2 x 10(7) cells/mL, and antibody was produced continuously in a range of 260-280 mg/L in a stable long-term COT perfusion culture. The proposed new culture mode, the COT perfusion approach, guarantees the recovery of rCHO cells damaged by lowered temperature or high lactate and ammonium concentration. It will be an attractive choice for minimization of cell damage and stable long-term antibody production with high cell density.
The Extra-domain A of Fibronectin Is a Vascular Marker of Solid Tumors and Metastases (2007)

One of the most promising new avenues for the development of more selective and efficacious cancer therapies relies on the antibody-mediated targeted delivery of bioactive agents (e.g., cytokines) to the tumor environment. The identification of quantitative differences in the expression of accessible vascular proteins in metastatic lesions and host organs facilitate the development of antibody-based strategies, which should be highly efficient and selective, considering the fact that an over-exuberant neovasculature is a characteristic feature of aggressive cancers, and that tumor blood vessels are readily accessible for i.v. administered therapeutic agents. Metastasis is the main cause of death in cancer. The availability of metastasis-specific antigens accessible from the bloodstream will allow a selective delivery of therapeutic agents to metastatic lesions using antibodies as vehicles. Using a combination of vascular biotinylation of 129Sv mice bearing F9 liver metastases and mass spectrometry, we have identified 435 accessible proteins in metastasis and host organ specimens, of which 117 were exclusively detected in metastases. In particular, we found that the alternatively spliced extra-domain A (EDA) of fibronectin is strongly expressed in the neovasculature of liver metastases, while being undetectable in most normal organs. A human antibody to EDA was used to show EDA expression in the neovasculature of metastases and primary tumors of human cancer patients and to target mouse liver metastases and subcutaneous tumors in vivo. Human antibody fragments specific to the EDA domain of fibronectin promise to serve as general vehicles for the efficient and selective delivery of imaging agents or therapeutic molecules to metastatic sites.
DNA binding properties of an HMG1-related protein from yeast mitochondria. (1992)

The DNA binding properties of ABF2, an abundant protein found in the mitochondria of the yeast Saccharomyces cerevisiae have been examined in detail. ABF2 is closely related to the vertebrate high mobility group protein HMG1 and like HMG1, ABF2 will introduce negative supercoils into a relaxed, double-stranded circular DNA molecule in cooperation with a DNA topoisomerase. Additionally, ABF2 binds approximately 5-10 times more tightly to negatively supercoiled DNA than to relaxed circular or linear DNA. Although ABF2 binds to most random double-stranded sequences with roughly equal affinity, its binding within certain key regulatory regions is qualitatively quite different. First, ABF2 binding induces a distinct pattern of DNA bending within the chromosomal origin of DNA replication, ARS1. Second, ABF2 binding to all nuclear replication origins tested, in addition to a critical mitochondrial promoter and replication origin, is clearly nonrandom as visualized by DNase1 footprinting. Analysis of the sequences found within these regions as well as competition experiments with synthetic DNA molecules suggest that site-specific DNA binding may be accomplished by the phased distribution of short stretches of poly(dA), which exclude ABF2 binding. These patterns of ABF2 DNA binding suggest a role for the protein in genome organization and site-specific regulation of transcription or DNA replication.
Downregulation of Multiple Stress Defense Mechanisms During Differentiation of Human Embryonic Stem Cells (2007)

Evolutionary theory predicts that cellular maintenance, stress defense, and DNA repair mechanisms should be most active in germ line cells, including embryonic stem cells that can differentiate into germ line cells, whereas it would be energetically unfavorable to keep these up in mortal somatic cells. We tested this hypothesis by examining telomere maintenance, oxidative stress generation, and genes involved in antioxidant defense and DNA repair during spontaneous differentiation of two human embryonic stem cell lines. Telomerase activity was quickly downregulated during differentiation, probably due to deacetylation of histones H3 and H4 at the hTERT promoter and deacetylation of histone H3 at hTR promoter. Telomere length decreased accordingly. Mitochondrial superoxide production and cellular levels of reactive oxygen species increased as result of increased mitochondrial biogenesis. The expression of major antioxidant genes was downregulated despite this increased oxidative stress. DNA damage levels increased during differentiation, whereas expression of genes involved in different types of DNA repair decreased. These results confirm earlier data obtained during mouse embryonic stem cell differentiation and are in accordance with evolutionary predictions.