gebhart/patrepeval huggingface dataset:
Stencils-based tutorials (2005)

Users of traditional tutorials and help systems often have difficulty finding the components described or pictured in the procedural instructions. Users also unintentionally miss steps, and perform actions that the documentation's authors did not intend, moving the application into an unknown state. We introduce Stencils, an interaction technique for presenting tutorials that uses translucent colored stencils containing holes that direct the user's attention to the correct interface component and prevent the user from interacting with other components. Sticky notes on the stencil's surface provide necessary tutorial material in the context of the application. In a user study comparing a Stencils-based and paper-based version of the same tutorial in Alice, a complex software application designed to teach introductory computer programming, we found that users of a Stencils-based tutorial were able complete the tutorial 26% faster, with fewer errors, and less reliance on human assistance. Users of the Stencils-based and paper-based tutorials attained statistically similar levels of learning.
Text Summarization Using Lexical Chains (2001)

Text summarization addresses both the problem of selecting the most important portions of text and the problem of generating coherent summaries. We present in this paper the summarizer of the University of Lethbridge at DUC 2001, which is based on an efficient use of lexical chains. 1
Active vaccination after allogeneic bone marrow cell transplantation: a new option in the immunotherapy of cancer? (2002)

The concept of immunotherapy of cancer was evoked more than a century ago by W. Coley. Yet it is only recently that the state of knowledge allows for molecularly defined therapeutic approaches and much effort will still be required to place immunotherapy beside of surgery, chemotherapy and radiation as a fourth option. In this review, we will focus chiefly on two aspects: active therapeutic vaccination, because it is our belief that this approach will provide a major breakthrough, and the potential efficacy of combining active vaccination with allogeneic bone marrow cell transplantation. It was recently established in clinical trials that allogeneic bone marrow cell transplantation does not require myeloablative conditioning. Non-myeloabaltive conditioning, which avoids the high toxicity of the conventional approach, it is only kind which allows the recruitment of elderly patients and patients in poor health. Concerning active vaccination protocols, we will address the questions 1) what the targets (i.e. the antigens) of immunotherapeutic approaches could be; 2) how to achieve an optimal confrontation of the immune system with these tumor-associated antigens; and 3) which response elements are needed for raising a therapeutically successful immune reaction against these antigens. Many question remain to be answered in the field of allogeneic bone marrow transplantation after non-myelablative conditioning to optimize the therapeutic setting for this, most likely, very powerful tool of cancer therapy. We will briefly summarize current considerations to improve engraftment, and reduce graft-versus-host disease while strengthening graft-versus-tumor reactivity. There is some hope that the latter can be "naturally" maintained during the process of T cell maturation in the allogeneic host. Provided this hypothesis can be substantiated, the efficacy of active vaccination of the allogeneically reconstituted host will provide a pool of virgin T cells which are tolerant towards the host, but not anergized towards tumor antigens presented by MHC molecules of the host. We will only briefly mention supportive regimen of immunomodulation and those hazards which one is most frequently confronted with in attempts to attack tumors with the inherent weapon of immune defense. Though the successful immunotherapy of cancer still remains far behind expectations, there is a solid basis for the belief that, by improving our understanding of the molecular mechanisms of immunity, this may become a very powerful and less harmful tool than conventional therapies.
Oxygen sensing and molecular adaptation to hypoxia (1996)

This review focuses on the molecular stratagems utilized by bacteria, yeast, and mammals in their adaptation to hypoxia. Among this broad range of organisms, changes in oxygen tension appear to be sensed by heme proteins, with subsequent transfer of electrons along a signal transduction pathway which may depend on reactive oxygen species. These heme-based sensors are generally two-domain proteins. Some are hemokinases, while others are flavohemoproteins [flavohemoglobins and NAD(P)H oxidases]. Hypoxia-dependent kinase activation of transcription factors in nitrogen-fixing bacteria bears a striking analogy to the phosphorylation of hypoxia inducible factor-1 (HIF-1) in mammalian cells. Moreover, redox chemistry appears to play a critical role both in the trans-activation of oxygen-responsive genes in unicellular organisms as well as in the activation of HIF-1. In yeast and bacteria, regulatory operons coordinate expression of genes responsible for adaptive responses to hypoxia and hyperoxia. Similarly, in mammals, combinatorial interactions of HIF-1 with other identified transcription factors are required for the hypoxic induction of physiologically important genes.
A disposable continuum endoscope using piston-driven parallel bellow actuator (2018)

This paper presents a novel low cost disposable continuum endoscope based on a piston-driven parallel bellow actuator design. The parallel bellow actuator achieves motion by being pressurized via displacement-controlled pistons. The displacements are generated by rack-and-pinion mechanisms using inexpensive stepper motors. The design concept provides a potential alternative solution to upper gastrointestinal (UGI) diagnosis. The modularity and the use of inexpensive components allow for low fabrication costs and disposability. The use of robotic assistance could facilitate the development of an easier interface for the gastroenterologists, avoiding the nonintuitive manipulation mapping of the traditional UGI endoscopes. We adapt existing kinematic solutions of multi-backbone continuum robots to model continuum parallel bellow actuators. An actuation compensation strategy is presented and validated to address the pneumatic compressibility through the transmission lines. The design concept was prototyped and tested with a custom control platform. The experimental validation shows that the actuation compensation was demonstrated to significantly improve orientation control of the endoscope end-effector. This paper shows the feasibility of the proposed design and lays the foundation toward clinical scenarios.
A 110‐kD nuclear shuttling protein, nucleolin, binds to the neurite‐promoting IKVAV site of laminin‐1 (1995)

The basement membrane protein laminin and the IKVAV-containing sequence from the laminin alpha 1 chain have been found to promote the differentiation of primary neurons and a variety of neural cell lines. We previously reported that a 110-kd IKVAV-binding protein (LBP110) isolated from brain appears to be a member of the beta-amyloid precursor protein (APP) family by immunologic and functional studies, which showed that LBP110/APP is also important in neurite outgrowth (Kibbey et al.: Proc Natl Acad Sci USA 90:10150-10153, 1993). In the preparation of this binding protein, a contaminating IKVAV-binding protein of identical molecular weight, nucleolin, was also identified. Here we have studied the relationship between these binding proteins. We find that nucleolin binds specifically to the IKVAV sequence independently of LBP110/ApP. We have also demonstrated significant levels of nucleolin in mature brain and in differentiating neural cells, suggesting that nucleolin functions not only in cell proliferation and in ribosome biogenesis as was previously reported, but also in the differentiation and maintenance of neural tissue. Our identification of cytoplasmic and cell-surface nucleolin, an IKVAV-binding protein, suggests that this protein may function in signalling by extra-cellular matrix.
2D back-side diffraction grating for improved light trapping in thin silicon solar cells (2010)

Light-trapping techniques can be used to improve the efficiency of thin silicon solar cells. We report on numerical investigation of a light trapping design consisting of a 2D back-side diffraction grating in combination with an aluminum mirror and a spacing layer of low permittivity to minimize parasitic absorption in the aluminum. The light-trapping design was compared to a planar reference design with antireflection coating and back-side aluminum mirror. Both normally and obliquely incident light was investigated. For normal incidence, the light trapping structure increases the short circuit current density with 17% from 30.4 mA/cm(2) to 35.5 mA/cm(2) for a 20 microm thick silicon solar cell. Our design also increases the current density in thinner cells, and yields higher current density than two recently published designs for cell thickness of 2 and 5 microm, respectively. The increase in current may be attributed to two factors; increased path length due to in-coupling of light, and decreased parasitic absorption in the aluminum due to the spacing layer.
Colloidal Aggregation Affects the Efficacy of Anticancer Drugs in Cell Culture (2012)

Many small molecules, including bioactive molecules and approved drugs, spontaneously form colloidal aggregates in aqueous solution at micromolar concentrations. Though it is widely accepted that aggregation leads to artifacts in screens for ligands of soluble proteins, the effects of colloid formation in cell-based assays have not been studied. Here, seven anticancer drugs and one diagnostic reagent were found to form colloids in both biochemical buffer and in cell culture media. In cell-based assays, the antiproliferative activities of three of the drugs were substantially reduced when in colloidal form as compared to monomeric form; a new formulation method ensured the presence of drug colloids versus drug monomers in solution. We also found that Evans Blue, a dye classically used to measure vascular permeability and to demonstrate the "enhanced permeability and retention (EPR) effect" in solid tumors, forms colloids that adsorb albumin, as opposed to older literature that suggested the reverse.
Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine (1993)

The (S)- and (R)-enantiomers of acyclic purine nucleoside phosphonate analogs (i.e., 3-hydroxy-2-phosphonomethoxypropyl [HPMP] derivatives, 3-fluoro-2-phosphonomethoxypropyl [FPMP] derivatives, and 2-phosphonomethoxypropyl [PMP] derivatives of adenine [A], 2-aminopurine, 2,6-diaminopurine [DAP], and guanine [G]) have been synthesized and evaluated for antiviral activity. As a rule, the HPMP derivatives proved effective against DNA viruses but not RNA viruses or retroviruses. In particular, (S)-HPMPA, (S)-HPMPDAP, and (R)- and (S)-HPMPG were exquisitely inhibitory to herpes simplex virus type 1 (50% effective concentrations, 0.63, 0.22, 0.10, and 0.66 microM, respectively). The FPMP and PMP derivatives showed marked inhibitory activities against retroviruses but not DNA viruses. The (S)-enantiomer of FPMPA and the (R)-enantiomer of PMPA were approximately 30- to 100-fold more effective against human immunodeficiency virus and Moloney murine sarcoma virus (MSV) than their enantiomeric counterparts. In contrast, both (S)- and (R)-enantiomers of the DAP and G derivatives proved equally effective against retroviruses, except for (R)-PMPDAP, which was 15- to 40-fold more inhibitory than (S)-PMPDAP. (R)-PMPDAP emerged as the most potent and selective inhibitor of MSV-induced transformation of murine C3H/3T3 cells and human immunodeficiency virus-induced cytopathicity in MT-4 and CEM cells (50% effective concentration, approximately 0.1 to 0.6 microM). When administered intraperitoneally at a single dose as low as 2 mg/kg, (R)-PMPDAP efficiently decreased MSV-induced tumor formation in newborn NMRI mice and significantly increased the survival time of MSV-infected mice. In addition, upon oral administration to MSV-infected mice, (R)-PMPDAP showed marked antiretroviral efficacy.
[Activated c-raf-1 gene from human stomach cancer]. (1987)

We previously isolated a novel human transforming sequence from a primary stomach cancer and identified the gene as an activated version of the c-raf-1 gene which is the human homologue of v-raf, a viral oncogene encoding a serine/threonine-specific protein kinase. Of 57 kbp of the human sequence isolated, a region of 40 kbp was found to be the minimum functional unit for the transforming activity, because a cosmid clone harboring this region was capable of inducing foci upon transfection. The size of the transcript of the transforming c-raf-1 gene was estimated to be about 2.8kb. Analyses of cDNA clones of this gene revealed that the gene was generated by substitution of the 5'-sequence (exons 1-5) of the normal c-raf-1 gene with an unrelated human sequence. We identified a region in the genomic clone where the rearrangement had occurred. The rearranged EcoRI fragment was detected in all the primary transformants obtained from two independent transfections, suggesting that the recombination had occurred in the primary cancer. The substituted cDNA sequence is composed of an open reading frame, which joins to exon 6 of the c-raf-1 gene in an in-phase manner. The substituted open reading frame encodes an extremely hydrophobic polypeptide. Thus, the putative product of the transforming gene seems to have a hydrophobic stretch ahead of the ser/thr-protein kinase domain of the c-raf-1 gene product. These results suggest that the truncation or replacement of the amino-terminal domain of the c-raf-1 protein leads to constitutive activation of the protein kinase residing in the downstream domain.
Cleavage of oligoribonucleotides by a ribozyme derived from the hepatitis .delta. virus RNA sequence (1992)

A self-cleaving RNA sequence from hepatitis delta virus was modified to produce a ribozyme capable of catalyzing the cleavage of RNA in an intermolecular (trans) reaction. The delta-derived ribozyme cleaved substrate RNA at a specific site, and the sequence specificity could be altered with mutations in the region of the ribozyme proposed to base pair with the substrate. A substrate target size of approximately 8 nucleotides in length was identified. Octanucleotides containing a single ribonucleotide immediately 5' to the cleavage site were substrates for cleavage, and cleavage activity was significantly reduced only with a guanine base at that position. A deoxyribose 5' to the cleavage site blocked the reaction. These data are consistent with a proposed secondary structure for the self-cleaving form of the hepatitis delta virus ribozyme in which a duplex forms with sequences 3' to the cleavage site, and they support a proposed mechanism in which cleavage involves attack on the phosphorus at the cleavage site by the adjacent 2'-hydroxyl group.
A critique of European Standard EN 15251: strengths, weaknesses and lessons for future standards (2011)

European Standard EN 15251 has broken new ground. Firstly, it assembles existing information about optimizing thermal, air quality, acoustic and visual comfort so that designers can make energy calculations which embody all the best information about aspects of the environment that impinge on energy use. Secondly, it follows other standards in recognizing the different expectations occupants have of the thermal environment in mechanically and naturally ventilated buildings. Potentially this makes EN 15251 an important standard in the design and the evaluation of new and existing buildings. Therefore, it is essential to be clear about its strengths and weaknesses and to indicate ways in which future updates might improve on it. This paper considers the way in which the Standard is written, its underlying philosophy and purpose, and the ways in which it defines unacceptable thermal conditions and how they might be misunderstood. Questions are raised regarding the use of outdoor temperature to define indoor comfort as the basis for providing a comfortable indoor thermal environment. Suggestions are made for improving the Standard. La norme européenne EN 15251 marque de nouvelles avancées. En premier lieu, elle rassemble les informations existantes relatives à l'optimisation du confort thermique, acoustique, visuel et lié à la qualité de l'air, de façon à permettre aux concepteurs d'effectuer des calculs énergétiques qui soient l'expression du meilleur des informations relatives aux aspects environnementaux qui affectent l'utilisation de l'énergie. En deuxième lieu, cette norme suit les autres normes en ce qu'elle reconnaît les différentes attentes qui sont celles des occupants en matière d'environnement thermique dans des immeubles à ventilation mécanique et naturelle. Cela fait potentiellement de la norme EN 15251 une norme importante pour la conception et l'évaluation des immeubles neufs et existants. Il est par conséquent essentiel d'en montrer clairement les points forts et les points faibles et d'indiquer les moyens par lesquels de futures mises à jour pourraient y apporter des améliorations. Le présent article examine la manière dont la norme est rédigée, la philosophie et le dessein qui la sous-tendent, ainsi que les façons dont elle définit les conditions thermiques qui ne sont pas acceptables et en quoi celles-ci pourraient être mal comprises. Des interrogations sont soulevées concernant le fait de se baser, pour assurer un environnement thermique intérieur confortable, sur l'utilisation de la température extérieure servant à définir le confort intérieur. Des suggestions sont faites pour l'amélioration de cette norme. Mots clés: confort thermique adaptatif normes de construction immeubles utilisation de l'énergie norme européenne EN 15251 normes
Architectural Implications of NAT (2000)

In light of the growing interest in, and deployment of network address translation (NAT) RFC-1631, this paper will discuss some of the architectural implications and guidelines for implementations. It is assumed the reader is familiar with the address translation concepts presented in RFC-1631.
THE role of indoleamine 2,3‐dioxygenase in the anti‐tumour activity of human interferon‐γ in vivo (1995)

We have studied the relationship between L-tryptophan metabolism and the response to human IFN-gamma in 3 human ovarian cancer xenografts growing in nude mice. During IFN-gamma therapy all 3 tumours showed a profound depletion in L-tryptophan and a corresponding rise in L-kynurenine. The microenvironment surrounding the tumours was also depleted of L-tryptophan. The IFN-gamma-inducible enzyme indoleamine dioxygenase, IDO, was induced in treated tumours. While there was a variability in IDO mRNA expression in the different xenografts tested, in situ hybridization showed that the gene was induced at all levels of the tumour, and not just the periphery. These results show that induction of IDO by IFN-gamma in vivo can metabolize L-tryptophan rapidly enough for it to become depleted, despite a continued supply of L-tryptophan from the host. The IDO mRNA and protein remained induced after the L-tryptophan levels had returned to normal, suggesting that the gene may be post-transcriptionally regulated and/or the IDO co-factor supply may be limited. Another IFN-gamma-inducible gene, tryptophanyl tRNA synthetase, was also induced in the tumour. It is possible that this enzyme, which is responsible for synthesizing tryptophanyl tRNA, acts in a compensatory manner by allowing protein synthesis to continue despite low free L-tryptophan concentrations. There was no correlation of the above parameters with the anti-tumour response to IFN-gamma, suggesting that other mechanisms must play a role. L-tryptophan depletion may be a contributor to a multifactorial growth inhibition of tumour cells following IFN-gamma treatment, but cannot on its own explain their growth inhibition.
Xanthones as antimalarial agents: stage specificity. (2000)

The erythrocytic development of Plasmodium falciparum is divided into the ring, trophozoite, and schizont stages based on morphologic assessment. Using highly synchronous ring and trophozoite cultures of P. falciparum, we observed considerable differences in their sensitivity to hydroxyxanthones: trophozoites were much more sensitive to the drugs than ring-stage parasites. Trophozoites treated with a prototypic xanthone, the 2,3,4,5,6-pentahydroxy derivative (X5), were arrested in their development and became degenerate in appearance within 24 hr of drug exposure. These morphologic changes appeared to reflect the cytotoxic nature of the action of the drug against the parasite, since daughter ring-stage forms were not observed following addition of the drug. That X5 was more active against parasites in the later stages of intraerythrocytic development is consistent with the proposed mode of action, inhibition of heme polymerization. Knowledge of the structure-activity relationships for xanthones as antimalarial agents has also been expanded. Xanthones with a hydroxyl group in the peri-position exhibited decreased antimalarial activity, possibly due to intramolecular hydrogen bonding with the carbonyl and consequent reduced affinity for heme. Paired hydroxyls attached to the lower half of the xanthone greatly enhanced drug potency.
A wild-type DNA ligase I gene is expressed in Bloom's syndrome cells. (1991)

Alteration of DNA ligase I activity is a consistent biochemical feature of Bloom's syndrome (BS) cells. DNA ligase I activity in BS cells either is reduced and abnormally thermolabile or is present in an anomalously dimeric form. To assess the role of DNA ligase function in the etiology of BS, we have cloned the DNA ligase I cDNA from normal human cells by a PCR strategy using degenerate oligonucleotide primers based on conserved regions of the Saccharomyces cerevisiae and Schizosaccharomyces pombe DNA ligase genes. Human DNA ligase I cDNAs from normal and BS cells complemented a S. cerevisiae DNA ligase mutation, and protein extracts prepared from S. cerevisiae transformants expressing normal and BS cDNA contained comparable levels of DNA ligase I activity. DNA sequencing and Northern blot analysis of DNA ligase I expression in two BS human fibroblast lines representing each of the two aberrant DNA ligase I molecular phenotypes demonstrated that this gene was unchanged in BS cells. Thus, another factor may be responsible for the observed reduction in DNA ligase I activity associated with this chromosomal breakage syndrome.