gebhart/patrepeval huggingface dataset:
Volume conformal irradiation of moving target volumes with scanned ion beams (2004)

The intensity modulated raster scanning technique enables an extremely precise irradiation of tumours, which can be fixed in position and do not move. This thesis investigates how to extend raster scanning to moving target volumes, like in the thorax. Two different strategies were studied: A rescanning of the volume which is not correlated to the target motion and an active realignment of the beam in all three dimensions during the irradiation (online motion compensation). The simulations and experiments concerning rescanning showed that the dose distribution can be improved in a limited part of the irradiation field, but the border area of the field remains strongly inhomogeneous. To improve the homogeneity over the whole target volume an extension of the irradiation field would be required, sacrificing volume conformity and increasing the dose contribution to the normal tissue in the tumour bed. The approach of active realignment of the beam during the irradiation avoids smearing of the dose distribution. In simulations the effect of different motion parameters on the dose homogeneity was calculated. Based on these calculations, a prototype for online motion compensation was constructed. In this setup the compensation of lateral motion components was realised with the scanning magnets. Longitudinal motion compensation was achieved with a fast, passive wedge system driven by linear motors. Both systems enabled an online realignment of the beam position with sub-millimetre precision. This prototype setup allowed the delivery of static dose distributions to targets, which were subject to respiration-like motion, with a precision of 1-2 %.
Simultaneous multicolor detection of RNA and proteins using super-resolution microscopy (2015)

A number of non-membranous cellular bodies have been identified in higher eukaryotes, and these bodies contain a specific set of proteins and RNAs that are used to fulfill their functions. The size of these RNA-containing cellular bodies is usually on a submicron scale, making it difficult to observe fine structures using optical microscopy due to the diffraction limitation of visible light. Recently, microscope companies have released super-resolution microscopes that were developed using different principles, enabling the observation of sub-micron structures not resolvable in conventional fluorescent microscopy. Here, we describe multi-color fluorescent in situ hybridization techniques optimized for the simultaneous detection of RNA and proteins using super-resolution microscopy, namely structured illumination microscopy (SIM).
Identification of pseudorabies virus-exposed swine with a gI glycoprotein enzyme-linked immunosorbent assay (1989)

A monoclonal antibody specific for the gI glycoprotein of virulent pseudorabies virus was produced and used to affinity purify gI glycoprotein. The purified gI was used in an enzyme-linked immunosorbent assay (ELISA) that identified and differentiated field virus-exposed animals from animals vaccinated with gI-deleted virus. The gI ELISA was evaluated by comparing it with the virus neutralization test and with a standard ELISA which does not distinguish between vaccinated and naturally infected animals. Pigs vaccinated with a gI-deleted vaccine were seropositive by the virus neutralization or standard ELISA but were seronegative in the gI ELISA. Nonvaccinated and vaccinated animals were detected as seropositive in the gI ELISA only after exposure to gI-containing field virus. Exposed animals were detected as early as day 7 and for as long as 141 days after field virus exposure. As little as 10(2.7) PFU of field virus was sufficient to seroconvert negative animals in the gI ELISA. Pseudorabies virus-seronegative animals which received multiple doses of gI-deleted vaccine remained seronegative in the gI ELISA. The use of this test to monitor swine for pseudorabies virus infection would offer significant benefits towards eradication of the disease.
Stability of clavulanic acid in aqueous solutions. (1981)

The stability of clavulanic acid in aqueous solutions has been investigated over a pH range of 3.15 to 10.10 at 35°C and at an ionic strength of 0.5. The changes in the concentration of intact clavulanic acid in buffer solutions were determined by reversed phase HPLC with UV-detection using a mobile phase containing tetrabutylammonium bromide. The observed degradation rates at various pH's were found to follow pseudo-first-order kinetics, and were significantly affected by catalysis due to buffer salts. The catalytic rate constants were estimated at three different concentrations of buffer systems. The pH vs. rate profiles obtained from non-buffer-catalyzed rate constants, kpH, revealed that the degradation in alkaline solutions proceeded, as a whole, about 10 times faster than in acidic media, and maximal stability was attained at pH 6.39. The Arrhenius activation energies at pH 3.94, 6.67, and 8.74 were estimated as 19.0, 14.7, and 18.3 kcal/mol, respectively.
Localization of difficult-to-translate phrases (2007)

This paper studies the impact that difficult-to-translate source-language phrases might have on the machine translation process. We formulate the notion of difficulty as a measurable quantity; we show that a classifier can be trained to predict whether a phrase might be difficult to translate; and we develop a framework that makes use of the classifier and external resources (such as human translators) to improve the overall translation quality. Through experimental work, we verify that by isolating difficult-to-translate phrases and processing them as special cases, their negative impact on the translation of the rest of the sentences can be reduced.
Butyrate augments interferon-α-induced S phase accumulation and persistent tyrosine phosphorylation of cdc2 in K562 cells (1999)

Interferon-alpha (IFN-alpha) is a clinically useful cytokine for treatment of a variety of cancers, including chronic myelocytic leukaemia (CML). Most CML cells are sensitive to IFN-alpha; however, its biological effects on leukaemic cells are incompletely characterized. Here, we provide evidence that IFN-alpha induces a significant increase in the S phase population in human CML leukaemic cell line, K562, and that the S phase accumulation was augmented by sodium butyrate. In contrast, neither sodium butyrate alone, nor sodium butyrate plus IFN-gamma, affected the cell cycle in K562 cells. These data suggest that the effect of sodium butyrate depended upon IFN-alpha-mediated signalling. The ability of leukaemic cells to exhibit the S phase accumulation after stimulation by IFN-alpha plus sodium butyrate correlated well with persistent tyrosine phosphorylation of cdc2, whereas treatment with IFN-gamma plus sodium butyrate did not affect its phosphorylation levels. Considering that dephosphorylation of cdc2 leads to entry to the M phase, the persistent tyrosine phosphorylation of cdc2 may be associated with the S phase accumulation induced by IFN-alpha and sodium butyrate. In addition, another human CML leukaemic cell line, MEG-01, also showed the S phase accumulation after stimulation with IFN-alpha plus sodium butyrate. Taken together, our studies reveal a novel effect of sodium butyrate on the S phase accumulation and suggest its clinical application for a combination therapy with IFN-alpha, leading to a great improvement of clinical effects of IFN-alpha against CML cells.
Retinitis pigmentosa and retinal neovascularization: a case report. (1984)

A 21-year-old white man with retinitis pigmentosa was found to have an isolated patch of retinal neovascularization. Ocular and systemic evaluation failed to reveal a recognized cause for the neovascularization. This case is felt to represent the unusual association of retinitis pigmentosa and retinal neovascularization.
PF-03814735, an Orally Bioavailable Small Molecule Aurora Kinase Inhibitor for Cancer Therapy (2010)

The Aurora family of highly related serine/threonine kinases plays a key role in the regulation of mitosis. Aurora1 and Aurora2 play important but distinct roles in the G(2) and M phases of the cell cycle and are essential for proper chromosome segregation and cell division. Overexpression and amplification of Aurora2 have been reported in different tumor types, including breast, colon, pancreatic, ovarian, and gastric cancer. PF-03814735 is a novel, potent, orally bioavailable, reversible inhibitor of both Aurora1 and Aurora2 kinases that is currently in phase I clinical trials for the treatment of advanced solid tumors. In intact cells, the inhibitory activity of PF-03814735 on the Aurora1 and Aurora2 kinases reduces levels of phospho-Aurora1, phosphohistone H3, and phospho-Aurora2. PF-03814735 produces a block in cytokinesis, resulting in inhibition of cell proliferation and the formation of polyploid multinucleated cells. Although PF-03814735 produces significant inhibition of several other protein kinases, the predominant biochemical effects in cellular assays are consistent with inhibition of Aurora kinases. Once-daily oral administration of PF-03814735 to mice bearing human xenograft tumors produces a reduction in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition. These results support the clinical evaluation of PF-03814735 in cancer patients. Mol Cancer Ther; 9(4); 883-94. (c)2010 AACR.
Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. (1996)

Although cyclin-dependent kinase 5 (Cdk5) is closely related to other cyclin-dependent kinases, its kinase activity is detected only in the postmitotic neurons. Cdk5 expression and kinase activity are correlated with the extent of differentiation of neuronal cells in developing brain. Cdk5 purified from nervous tissue phosphorylates neuronal cytoskeletal proteins including neurofilament proteins and microtubule-associated protein tau in vitro. These findings indicate that Cdk5 may have unique functions in neuronal cells, especially in the regulation of phosphorylation of cytoskeletal molecules. We report here generation of Cdk5(-/-) mice through gene targeting and their phenotypic analysis. Cdk5(-/-) mice exhibit unique lesions in the central nervous system associated with perinatal mortality. The brains of Cdk5(-/-) mice lack cortical laminar structure and cerebellar foliation. In addition, the large neurons in the brain stem and in the spinal cord show chromatolytic changes with accumulation of neurofilament immunoreactivity. These findings indicate that Cdk5 is an important molecule for brain development and neuronal differentiation and also suggest that Cdk5 may play critical roles in neuronal cytoskeleton structure and organization.
Percutaneous coronary intervention. I: History and development (2003)

The term “angina pectoris” was introduced by Heberden in 1772 to describe a syndrome characterised by a sensation of “strangling and anxiety” in the chest. Today, it is used for chest discomfort attributed to myocardial ischaemia arising from increased myocardial oxygen consumption. This is often induced by physical exertion, and the commonest aetiology is atheromatous coronary artery disease. The terms “chronic” and “stable” refer to anginal symptoms that have been present for at least several weeks without major deterioration. However, symptom variation occurs for several reasons, such as mental stress, ambient temperature, consumption of alcohol or large meals, and factors that may increase coronary tone such as drugs and hormonal change.

View this table:

Unequivocal indications for use of coronary stents



The Canadian Cardiovascular Society has provided a graded classification of angina which has become widely used. In clinical practice, it is important to describe accurately specific activities associated with angina in each patient. This should include walking distance, frequency, and duration of episodes.

In the management of chronic stable angina, there are two invasive techniques available for myocardial revascularisation: coronary artery bypass surgery and catheter attached devices. Although coronary artery bypass surgery was introduced in 1968, the first percutaneous transluminal coronary angioplasty was not performed until September 1977 by Andreas Gruentzig, a Swiss radiologist, in Zurich. The patient, 38 year old Adolph Bachman, underwent successful angioplasty to a left coronary artery lesion and remains well to this day. After the success of the operation, six patients were successfully treated with percutaneous transluminal coronary angioplasty in that year.

By today's standards, the early procedures used cumbersome equipment: guide catheters were large and could easily traumatise the vessel, there were no guidewires, and balloon catheters were large with low burst pressures. As a result, the procedure was limited to patients with refractory angina, good …
Selective Primary Health Care: Strategies for Control of Disease in the Developing World. XI. Dengue (1984)

Since World War II, dengue viruses have progressively extended their geographic domain and have increased as causes of human morbidity and mortality. This complex of four flaviviruses is principally transmitted to humans by the bite of Aedes aegypti, the yellow fever vector. Factors that promote the indoor storage of water are congenial to the breeding of A. aegypti. These include the dislocations of wars, overpopulation , and urbanization. By the mid-20th century, A. aegypti eradication campaigns had nearly succeeded in much of the Western Hemisphere. Since then, there has been a steady degradation in ability to cope with this species despite the fact that a newly emerged, severe immunopathologic disorder, dengue hemorrhagic fever/dengue shock syndrome, endows dengue epidemics with grave consequences. Development of a vaccine against dengue is complicated by the need to develop four different live attenuated vaccines and by a justifiable caution imposed by dengue immunopathology. A wide range of proven methods have been and are available to reduce populations of A. aegypti. This paper argues that the eradication strategy adopted earlier in this century is still viable and cost effective. Critical to a successful control program is a prioritied approach, a thorough, disciplined planning effort, a commitment to assessment, adequate compensation of staff, and, above all, the will to succeed.
Design and synthesis of curcumin-bioconjugates to improve systemic delivery (2000)

Di-O-glycinoyl curcumin (I), di-O-glycinoyl-C4-glycyl-curcumin (II), 5'-deoxy-5'-curcuminyl thymidine (5'-cur-T) (III) and 2'-deoxy-2'-curcuminyl uridine (2'-cur-U) (IV) have been synthesized and characeterised by elemental analysis & 1H NMR. The antibacterial activities of these four bioconjugates has been tested particularly for multiresistant micro-organisms. Best results are shown by I & IV. These bioconjugates serve dual purpose of systemic delivery as well as therapeutic agents against viral diseases.
Phage display of peptides and proteins : a laboratory manual (1996)

Biology of the filamentous bacteriophage, B. Webster principles and applications of phage display, B.K. Kay and R.H. Hoess vectors for phage display, N.B. Adey, S.J. McConnell, and B.K. Kay construction of random peptide libraries in bacteriophage M13, A.B. Sparks, N.B. Adey, J. Beasley, and B.K. Kay construction and screening of antibody display libraries, J. McCafferty and K. Johnson phagemid-displayed peptide libraries, D. Dottavio and J. Winter phage libraries displaying random peptides derived from a target sequence, D.H. du Plessis and F. Jordaan display and selection of proteins on genetic packages, R.C. Ladner a cDNA cloning system based on filamentous phage - selection and enrichment of functional gene products by protein/ligand interactions made possible by linkage of recognition and replication functions, M. Suter, M. Foti, M. Ackermann, and R. Crameri multicombinatorial libraries and combinatorial infection - practical considerations for vector design, R. Sudoyer use of filamentous virus particles as immunogens, R. Perham screening phage displayed random peptide libraries, A.B. Sparks, N.B. Adey, S. Cwirla, and B.K. Kay substrate phage, D. Matthews phage display - factors affecting planning efficiency, J. McCafferty preparation of second generation phage libraries, N.B. Adey, W.P.C. Stemmer, and B.K. Kay nonradioactive sequencing of random peptide recombinant phage, B.L. Masecar, C.A. Dadd, G.A. Baumbach, and D.J. Hammond measurement of peptide binding affinities using fluorescence polarization, T. Burke, R. Bolger, W. Checovich, and R. Lowery.
Non-Nucleoside Inhibitors of BasE, an Adenylating Enzyme in the Siderophore Biosynthetic Pathway of the Opportunistic Pathogen Acinetobacter baumannii (2013)

Siderophores are small-molecule iron chelators produced by bacteria and other microorganisms for survival under iron limiting conditions such as found in a mammalian host. Siderophore biosynthesis is essential for the virulence of many important Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. We performed high-throughput screening against BasE, which is involved in siderophore biosynthesis in A. baumannii, and identified 6-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid 15. Herein we report the synthesis, biochemical, and microbiological evaluation of a systematic series of analogues of the HTS hit 15. Analogue 67 is the most potent analogue with a KD of 2 nM against BasE. Structural characterization of the inhibitors with BasE reveals that they bind in a unique orientation in the active site, occupying all three substrate binding sites, and thus can be considered as multisubstrate inhibitors. These results provide a foundation for future studies aimed at increasing both enzyme potency and antibacterial activity.
Loss aversion and risk taking in mediation (2002)

Extract: At the heart of every family mediation is the issue of loss. Every family mediator deals with their clientsâ losses, whether perceived or actual. Most people in mediation are already acutely aware of having their lives wrenched apart by the ending of their relationship, especially those who are left behind by their former partner.
[Clinical analysis of orbital cysticercus cellulosae]. (1999)

We can make diagnosis by imaging tests and treat them with surgical operations.
Methods of Fibrin Seal Application (1982)

With the help of various tests (tensile strength, distribution in cancellous bone blocks, thrombin release from standard clots), the importance of mixing the solutions of the fibrin sealant system was demonstrated and an optimal mixing ratio of one to one was identified. Different application techniques are discussed. The spraying technique, which produces rapid hemostasis, is reviewed in detail. As further advantage, the resulting sealant film is thin. This appears important for promoting wound healing.
Intelligent buildings and their effect on the security industry (2002)

Behind all of the hype of intelligent superhighways, developments to make our homes and offices more intelligent have been gaining pace and several prominent systems are now available on the market. These are generally based on the introduction into the building of (sets of) homogeneous bus systems which then control a wide variety of functions (heating, lighting, AV, etc.). It is a relatively easy step for such systems to include security. The significant opportunities to the management and sophistication of alarm systems that this affords are discussed, as are some dangers in the hands of the unwary.
Role of KRAS and EGFR As Biomarkers of Response to Erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21 (2008)

EGFR mutations and high copy number are predictive of response to erlotinib. EGFR FISH is the strongest prognostic marker and a significant predictive marker of differential survival benefit from erlotinib.
Identification and characterization of human taste receptor genes belonging to the TAS2R family (2002)

The sense of taste is a chemosensory system responsible for basic food appraisal. Humans distinguish between five primary tastes: bitter, sweet, sour, salty and umami. The molecular events in the perception of bitter taste are believed to start with the binding of specific water-soluble molecules to G-protein-coupled receptors encoded by the TAS2R/T2R family of taste receptor genes. TAS2R receptors are expressed at the surface of taste receptor cells and are coupled to G proteins and second messenger pathways. We have identified, cloned and characterized 11 new bitter taste receptor genes and four new pseudogenes that belong to the human TAS2R family. Their encoded proteins have between 298 and 333 amino acids and share between 23 and 86% identity with other human TAS2R proteins. Screening of a mono-chromosomal somatic cell hybrid panel to assign the identified bitter taste receptor genes to human chromosomes demonstrated that they are located in chromosomes 7 and 12. Including the 15 sequences identified, the human TAS2R family is composed of 28 full-length genes and 16 pseudogenes. Phylogenetic analyses suggest a classification of the TAS2R genes in five groups that may reflect a specialization in the detection of specific types of bitter chemicals.
Features of the chicken c-myc gene that influence the structure of c-myc RNA in normal cells and bursal lymphomas. (1986)

The chicken c-myc gene is the target for proviral insertion mutations in bursal lymphomas and has been transduced to generate several viral oncogenes, but the boundaries of its exons have not been securely established. To define the landmarks of the chicken c-myc gene necessary to produce its mRNA, we used an RNase protection assay and a cDNA clone to analyze the c-myc mRNAs from normal chicken embryos and from two bursal lymphomas: LL6, which contains an avian leukosis virus provirus downstream of the c-myc coding region, and LL7, which contains an avian leukosis virus provirus upstream of the c-myc coding region. Two initiation sites for normal c-myc mRNA are less than 7 bases apart, downstream of a GC-rich region lacking canonical TATA and CAAT sequences. The first exon has two open reading frames for the entire length but no initiator methionine codons. The splice donor and acceptor sites at the boundary of the first intron were assigned by comparing a sequence of an LL6 c-myc cDNA clone with a genomic DNA sequence and confirmed by RNase protection of labeled RNA probes by normal and LL6-derived mRNAs. Two potential polyadenylation signals are located approximately 250 and 400 bases downstream of the c-myc coding region in the third exon, but only the more distal signal is utilized in both normal cells and the LL7 tumor. The proviral integration in the LL6 tumor occurred upstream of the authentic c-myc polyadenylation signal accounting for polyadenylation of this transcript in the proviral long terminal repeat.