gebhart/patrepeval huggingface dataset:
Mechanisms of mutation by oxidative DNA damage: Reduced fidelity of mammalian DNA polymerase .beta. (1993)

Reactive oxygen species, produced in cells by a variety of mechanisms, damage DNA and cause mutations. To characterize the types of mutations produced in mammalian cells, we copied DNA damaged by reactive oxygen species with mammalian DNA polymerase beta. Double-stranded circular M13mp2 DNA containing a 361-nucleotide single-stranded gap within the lacZ gene was damaged by aerobic incubation with Fe2+ and H2O2. The gap then was filled by purified recombinant rat DNA polymerase beta, and the DNA was transfected into Escherichia coli. Mutations within the nonessential lacZ gene for beta-galactosidase were identified by reduced alpha-complementation. In this system, oxidative damage increased the mutation frequency within the target region by an average of 4.3-fold. At certain sites, the base substitution rate is nearly 300 times greater than would be expected to result from a random distribution of damage. The oxidatively induced mutations fall into two categories: those apparently caused by direct miscoding of modified DNA and those associated with enhanced misincorporation at prexisting polymerase-specific hot spots. The latter group may be due to a conformational change in the DNA caused by oxidative modification and could be indicative of a novel mutagenic mechanism.
Cleavage of DNA by R 1 Restriction Endonuclease Generates Cohesive Ends (1972)

R(1) restriction endonuclease cleaves duplex DNA at a specific sequence, probably 6 nucleotide pairs in length, by making two single-strand staggered cleavages, generating 5'-phosphoryl and 3'-hydroxyl termini. The single-strand ends produced at each break have identical and complementary sequences of 4 or 6 nucleotides in length. Therefore, the cleavage site possesses a 2-fold rotational axis of symmetry perpendicular to the helix axis. The ends of full-length linear SV40 DNA, generated by R(1) endonuclease cleavage, can be joined by Escherichia coli ligase to regenerate duplex, fully infectious, covalently-closed circular molecules. It was further found that all R(1) endonuclease-generated ends are identical and complementary. Therefore, any two DNA molecules with R(1) sites can be "recombined" at their restriction sites by the sequential action of R(1) endonuclease and DNA ligase to generate hybrid DNA molecules.
Parasympathetic Nervous System and Heart Failure (2008)

A bundant evidence links sympathetic nervous system activation to outcomes of patients with heart failure (HF). 1 In contrast, parasympathetic activation has complex cardiovascular effects that are only beginning to be recognized.][4][5] In the present article, we review cardiovascular responses to parasympathetic activation, address the modulating factors that can affect parasympathetic function, discuss the role of the vagus nerve in ventricular dysfunction, and consider how activation of the parasympathetic nervous system may have important therapeutic implications for patients with congestive HF. Structure of the Parasympathetic Limb of the Autonomic Nervous SystemThe parasympathetic nervous system originates from medial medullary sites (nucleus ambiguous, nucleus tractus solitarius, and dorsal motor nucleus) and is modulated by the hypothalamus.Vagal efferents extend from the medulla to postganglionic nerves that innervate the atria via ganglia located in cardiac fat pads with neurotransmission that is modulated via nicotinic receptors.Postganglionic parasympathetic and sympathetic cholinergic nerves then affect cardiac muscarinic receptors (the Figure ). 6 -8 Vagus nerve afferent activation, originating peripherally, can modulate efferent sympathetic and parasympathetic function centrally and at the level of the baroreceptor.Efferent vagus nerve activation can have tonic and basal effects that inhibit sympathetic activation and release of norepinephrine at the presynaptic level.Acetylcholine release from parasympathetic nerve terminals will activate ganglionic nicotinic receptors that in turn activate muscarinic receptors at the cellular level.Cardiovascular effects include heart rate reduction by inhibition of the sympathetic nervous system and by direct hyperpolarization of sinus nodal cells.Parasympathetic activation can affect atrioventricular nodal conduction mediated predominantly through the left vagus nerve.Furthermore, muscarinic receptors on blood vessel walls can cause vasorelaxation through a nitric oxide (NO)-modulated pathway but can also cause vasoconstriction by directly activating smooth muscle. 6 -8 Therefore, although the sympathetic nervous system has global effects on cardiovascular physiology in an all-or-none type of response, the parasympathetic nervous system can have selective modulation at various levels.
Learning hard concepts through constructive induction: framework and rationale (1990)

The intrinsic accuracy of an inductive problem is the accuracy achieved by exhaustive table look‐up. Intrinsic accuracy is the upper bound for any inductive method. Hard concepts are concepts that have high intrinsic accuracy, but which cannot be learned effectively with traditional inductive methods. To learn hard concepts, we must use constructive induction ‐ methods that create new features. We use measures of concept dispersion to explore (conceptually and empirically) the inherent weaknesses of traditional inductive approaches. These structural defects are buried in the design of the algorithms and prevent the learning of hard concepts. After studying some examples of successful and unsuccessful feature construction (“success” being defined here in terms of accuracy), we introduce a single measure of inductive difficulty that we call variation. We argue for a specific approach to constructive induction that reduces variation by incorporating various kinds of domain knowledge. All of these kinds of domain knowledge boil down to utility invariants, i.e., transformations that group together non‐contiguous portions of feature space having similar class‐membership values. Utility invariants manifest themselves in various ways: in some cases they exist in the user's stock of domain knowledge, in other cases they may be discovered via methods we describe.
Sequential strategy to identify a susceptibility gene for schizophrenia: Report of potential linkage on chromosome 22q12‐q13.1: Part 1 (1994)

To identify genes responsible for the susceptibility for schizophrenia, and to test the hypothesis that schizophrenia is etiologically heterogeneous, we have studied 39 multiplex families from a systematic sample of schizophrenic patients. Using a complex autosomal dominant model, which considers only those with a diagnosis of schizophrenia or schizoaffective disorder as affected, a random search of the genome for detection of linkage was undertaken. Pairwise linkage analyses suggest a potential linkage (LRH = 34.7 or maximum lod score = 1.54) for one region (22q12-q13.1). Reanalyses, varying parameters in the dominant model, maximized the LRH at 660.7 (maximum lod score 2.82). This finding is of sufficient interest to warrant further investigation through collaborative studies.
Clustering metagenomic sequences with interpolated Markov models (2010)

SCIMM and PHYSCIMM are highly accurate methods to cluster metagenomic sequences. SCIMM operates entirely unsupervised, making it ideal for environments containing mostly novel microbes. PHYSCIMM uses supervised learning to improve clustering in environments containing microbial strains from well-characterized genera. SCIMM and PHYSCIMM are available open source from http://www.cbcb.umd.edu/software/scimm.
The Evaluation Incidence and Risk Factors of Mortality among Patients with End Stage Renal Disease in Southeast Turkey (2008)

CVD are the most important preventable causes of morbidity and mortality in all stages of chronic kidney disease. Taking precaution against CVD and the associated complications will provide a positive contribution in reducing morbidity and mortality among ESRD patients.
Modulation of Soluble CD40 Ligand Bioactivity with Anti-CD40 Antibodies (1997)

The B cell surface molecule CD40 may be activated either by its ligand CD40L or by anti-CD40 antibodies. In this study, five new anti-CD40 monoclonal antibodies (MAb) were characterized. Bioactivity of the MAb was assessed using a receptor hybrid consisting of the extracellular domain of CD40 and the intracellular domain of the p55 TNF receptor as a model for CD40 activation. Two agonistic MAb were able to enhance the activation of this CD40 hybrid CD40L. These MAb bound to an epitope that was not located within the CD40L-binding region indicating that activation of CD40 occurs epitope-independent. A second pair of ligand mimetic anti-CD40 MAb which appeared to bind to the CD40L binding site decreased CD40L bioactivity. With regard to ligand mimetic effects binding of the CD40L epitope was not of advantage. Combining anti-CD40 MAb with different epitope specificities or cross linking anti-CD40 MAB with secondary antibodies enhanced ligand mimetic effects. These data clearly show that ligand or antibody-mediated receptor aggregation is the major mechanism by which CD40 is activated. Furthermore, our data support that an aggregate of activated receptors is favorable in regard to CD40 activation.
Stimulated Acoustic Emission Detected by Transcranial Color Doppler Ultrasound (2000)

Echo-contrast specific color Doppler signals known as SAE are detectable by transcranial color and power Doppler sonography. Signals due to SAE might represent tissue perfusion, thereby providing a method for imaging flow with transcranial ultrasound.
Can continuous glucose monitoring be used for the treatment of diabetes? (1992)

In the case of the glucose sensor, clinicians and chemists must cooperate in interdisciplinary research to carefully define the analytical problem. Although not specifically discussed in this article, another group that must participate in this effort is engineers. Their expertise is needed to design the monitoring and control unit that contains the alarm and pump systems. The glucose sensor must operate reliably in an in vivo environment, provide the clinical information needed, and be easy to operate and manufacture.
Transporter Gene Expression in Human Head and Neck Squamous Cell Carcinoma and Associated Epigenetic Regulatory Mechanisms (2012)

Expression levels of membrane transporters may affect the disposition, and thereby treatment efficacy, of anticancer drugs in human head and neck squamous cell carcinoma (HNSCC). Herein, we analyzed the gene expression profile of membrane transporters in HNSCC. In addition, we evaluated the mechanisms of transporter regulation in HNSCC and focused on the role of the nuclear pregnane X receptor (or NR1I2) and epigenetic mechanisms. Real-time RT-PCR revealed a significantly increased mRNA expression of membrane transporters SLCO1A2 and SLCO1B3 and a significantly decreased expression of transporters SLCO2B1, SLCO2A1, and ABCC3 in human HNSCC tumors compared with adjacent normal mucosa. An association between SLCO2B1 mRNA levels in tumors and 5-year survival of patients with HNSCC was observed (χ2 = 6.59, P = 0.010). Bisulfite sequencing revealed that promoter CpG islands of ABCC3 and SLCO2A1 were not hypermethylated, indicating that these genes were not epigenetically silenced in HNSCC tumors. In HNSCC-derived cell lines, transcript expression of transporters (e.g., ABCC3 or SLCO2A1; P < 0.001 for both) and NR1I2 (P < 0.001) was markedly induced by the DNA methyltransferase inhibitor, decitabine. Cotreatment with the prototypical pregnane X receptor activator, rifampicin, significantly reversed decitabine-induced ABCC3 and SLCO2A1 expression. In summary, the expression of drug transporters (i) is markedly changed in HNSCC tumor tissues compared with normal mucosa, (ii) might be predictive of the outcome of patients with HNSCC, and (iii) is affected by novel epigenetic therapies and is further modulated by nuclear receptor-mediated mechanisms.
Multivalent antibody fragments with high functional affinity for a tumor-associated carbohydrate antigen (1996)

We report in this work a human-derived self-assembling polypeptide based on the tetramerization domain of the human transcription factor p53, which can be fused to single-chain Fv Ab (scFv) fragments via a long and flexible hinge sequence of human origin, allowing exploitation of the functional affinity increase of binding to a ligand or cell surface with multimeric binding sites. We have demonstrated the use of this polypeptide by applying it to the construction of a tetrameric scFv against the tumor-associated carbohydrate Ag Lewis Y (Fuc alpha 1-->2Gal beta 1-->4[Fuc alpha 1-->3] GlcNAc beta 1-->3R). For comparison purposes, the corresponding scFv and dimeric mini-antibody, comprising the scFv fused via a flexible murine hinge to an artificial dimerization domain, were also created. The recombinant mini-antibody proteins were expressed in functional form in Escherichia coli and showed the expected m.w. of a dimer and tetramer, respectively. Analysis of Lewis Y-binding behavior by surface plasmon resonance revealed specific but very weak binding of the scFv fragment. In contrast, both dimeric and tetrameric scFv fusion proteins exhibited an enormous gain in functional affinity that was greatest in the case of the tetrameric mini-antibody.
Pharmacokinetics, dosimetry, and initial therapeutic results with 131I- and (111)In-/90Y-labeled humanized LL2 anti-CD22 monoclonal antibody in patients with relapsed, refractory non-Hodgkin's lymphoma. (1999)

The pharmacokinetics, dosimetry, and immunogenicity of 131I- and (111)In-/90Y-humanized LL2 (hLL2) anti-CD22 monoclonal antibodies were determined in patients with recurrent non-Hodgkin's lymphoma. Fourteen patients received tracer doses of 131I-hLL2 followed 1 week later by therapeutic doses intended to deliver 50-100 cGy to the bone marrow. Another eight patients received (111)In-hLL2 followed by therapy with 90Y-hLL2 also delivering 50 or 100 cGy to the bone marrow. The blood T(1/2) (hours) for the tracer infusions of 131I-hLL2 was 44.2 +/- 10.9 (mean +/- SD) compared with 54.2 +/- 25.0 for the therapy infusions, whereas the values were 70.7 +/- 17.6 for (111)In-hLL2 and 65.8 +/- 15.0 for 90Y-hLL2. The estimated average radiation dose from 131I-hLL2 in tumors >3 cm was 2.4 +/- 1.9 cGy/mCi and was only 0.9-, 1.0-, 1.1-, and 1.0-fold that of the bone marrow, lung, liver, and kidney, respectively. In contrast, the estimated average radiation dose from 90Y-hLL2 in tumors >3 cm was 21.5 +/- 10.0 cGy/mCi and was 3.7-, 2.5-, 1.8-, and 2.5-fold that of the bone marrow, lung, liver, and kidney, respectively. No evidence of significant anti-hLL2 antibodies was seen in any of the patients. Myelosuppression was the only dose-limiting toxicity and was greater in patients who had prior high-dose chemotherapy. Objective tumor responses were seen in 2 of 13 and 2 of 7 patients given 131I-hLL2 or 90Y-hLL2, respectively. In conclusion, 90Y-hLL2 results in a more favorable tumor dosimetry compared with 131I-hLL2. This finding, combined with the initial anti-tumor effects observed, encourage further studies of this agent in therapeutic trials.
Influences of Lewis Acids on the Photochemical Cyclodimerization of Cyclopentenone (1987)

Abstract In the presence of tin(IV) chloride, photochemical dimerization of cyclopentenone gave a cis-transoid-cis head-to-head dimer as predominant product. Other Lewis acids such as zinc(II) bromide, boron trifluoride etherate, tin(II) chloride, and silver(I) trifluoromethylsulfonate, however, showed little influence. Tris(2,2,6,6-tetramethyl-3,5-heptanedionato)lanthanum(III) andtris(2,2,6,6-tetramethyl-3,5-heptanedionato)europium(III) affected regiochemistry of the reaction in a way to favor a head-to-tail dimer.
CSF-1 signal transduction (1997)

Colony-stimulating factor-1 (CSF-1) or macrophage-CSF (M-CSF) is a growth factor involved in the proliferation, differentiation, and activation of cells of the monocyte/macrophage lineage. Its receptor is the homodimeric, tyrosine kinase product of the c-fms proto-oncogene, which contains a so-called kinase insert domain. This review focuses mainly on recent studies of signal transduction events that are initiated on interaction of CSF-1 and its receptor. A summary is given of the tyrosine autophosphorylation sites on c-Fms identified to date, including their interaction with various substrates and their possible significance for signal transduction and cellular function. In addition, the signal transduction pathways that have been identified to lie downstream of activated c-Fms are reviewed. Although it is apparent that there have been many recent significant developments in our understanding of CSF-1 signaling, a number of examples are mentioned of significant discrepancies in the literature, some possible reasons for which can sometimes be offered. It is also apparent that any particular biochemical response or signal transduction pathway, even though widespread in other ligand receptor/cellular systems, including those with similar receptor structures to c-Fms, may not be relevant to CSF-1 signaling. The relevance of any potentially important molecular signaling pathway activated by CSF-1 in cells in vitro will ultimately have to be related to the functions of monocytes/macrophages in vivo.
Poly(lactide) Stereocomplexes: Formation, Structure, Properties, Degradation, and Applications (2005)

Poly(lactide)s [i.e. poly(lactic acid) (PLA)] and lactide copolymers are biodegradable, compostable, producible from renewable resources, and nontoxic to the human body and the environment. They have been used as biomedical materials for tissue regeneration, matrices for drug delivery systems, and alternatives for commercial polymeric materials to reduce the impact on the environment. Since stereocomplexation or stereocomplex formation between enantiomeric PLA, poly(L-lactide) [i.e. poly(L-lactic acid) (PLLA)] and poly(D-lactide) [i.e. poly(D-lactic acid) (PDLA)] was reported in 1987, numerous studies have been carried out with respect to the formation, structure, properties, degradation, and applications of the PLA stereocomplexes. Stereocomplexation enhances the mechanical properties, the thermal-resistance, and the hydrolysis-resistance of PLA-based materials. These improvements arise from a peculiarly strong interaction between L-lactyl unit sequences and D-lactyl unit sequences, and stereocomplexation opens a new way for the preparation of biomaterials such as hydrogels and particles for drug delivery systems. It was revealed that the crucial parameters affecting stereocomplexation are the mixing ratio and the molecular weight of L-lactyl and D-lactyl unit sequences. On the other hand, PDLA was found to form a stereocomplex with L-configured polypeptides in 2001. This kind of stereocomplexation is called "hetero-stereocomplexation" and differentiated from "homo-stereocomplexation" between L-lactyl and D-lactyl unit sequences. This paper reviews the methods for tracing PLA stereocomplexation, the methods for inducing PLA stereocompelxation, the parameters affecting PLA stereocomplexation, and the structure, properties, degradation, and applications of a variety of stereocomplexed PLA materials.
Shunting (2007)

Stateful, in-depth, inline traffic analysis for intrusion detection and prevention is growing increasingly more difficult as the data rates of modern networks rise. Yet it remains the case that in many environments, much of the traffic comprising a high-volume stream can, after some initial analysis, be qualified as of "likely uninteresting." We present a combined hardware/software architecture, Shunting, that provides a lightweight mechanism for an intrusion prevention system (IPS) to take advantage of the "heavy-tailed" nature of network traffic to offload work from software to hardware.
OMF-an object request broker for the process control application domain (1999)

Long before middleware became a market topic and professional providers offered out of the box functionality, industry like Asea Brown Boveri (ABB), had to provide solutions, which were based on what we today call middleware. Consequently, many industrial firms developed their own solutions. We describe an ABB proprietary middleware product called Object Management Facility (OMF). We present all its architectural properties and functional features. Wherever meaningful, we compare OMF's abilities with those offered by DCOM and CORBA and for some aspects important to the domain of control systems, we show that even today, OMF can compete with commercially available middleware products.
Escherichia coli mutator mutants deficient in methylation-instructed DNA mismatch correction. (1980)

Our approach to the isolation of DNA mismatch-correction-deficient mutants was based upon the isolation of 2-aminopurine-resistant second-site revertants of Escherichia coli dam- mutants. We isolated such second-site revertants which, when separated from the dam- mutation, have a mutator character of their own. These new mutators all mapped at three known mutator loci, mutH, mutL, and mutS, which exhibit the same mutagenic spectrum as the dam- mutator: increased levels of base substitution and frameshift mutations. The mutator potencies of double and triple mut- mutants suggest that these mutators are involved in the same general mismatch-repair pathway. All these mutations result in a hyper-recombination phenotype, but in four-factor crosses among lambda phages, a specific loss of intragenic recombination (Pam3 X Pam80) was found in mutL and mutS mutants, as would be predicted from the postulated role of mismatch correction in gene conversion and high negative interference phenomena.
Transmucosal Administration of Midazolam for Premedication of Pediatric Patients (1993)

Sublingual administration of midazolam is as effective as, and better accepted than, intranasal midazolam as a preanesthetic sedative in children.
Subscription Teletext for Value Added Services (1985)

Teletext is rapidly becoming a household name in many countries in Europe. Its success is partly because it can provide instant information to anyone with a suitable decoder free of charge. In the UK, teletext services are financed either from the licence fee (Ceefax) or from advertising revenue (Oracle). Videotex systems such as Prestel make use of the public telephone network and are interactive and can be financed by charging the user directly. The user pays for the telephone connection, computer time and the information. These costs can be prohibitive particularly when terminals remain connected throughout the day.
Gene therapy: Fact and fiction in biology's new approaches to disease (1983)

In 1982, a meeting of unusual influence was held at the Banbury Conference Center of Cold Spring Harbor Laboratory. After an early attempt at treating clinical disease with transferred genes had ignited public attention and scientific controversy, a group of distinguished biologists and physicians came together to assess practical progress towards gene therapy and what its future might be. The geneticist Ted Friedmann wrote a narrative account of the participants' contributions to the meeting, ending with a personal discussion of ethical issues raised by genetic technologies. His book, the first on gene therapy, was widely read but has long been unavailable. It has been reprinted with a new introduction entitled Gene Therapy 1994, in which the author reviews the field's technical accomplishments and ethical dilemmas. Now that gene therapy has become part of the medical landscape, this volume is of interest as both a historical document and an assessment of the field's current challenges.