gebhart/patrepeval huggingface dataset:
On the shoulders of giants : Kuhn on paradigm shifts (2009)

When a paradigm shift occurs in the industry, the present business model markedly changes by the introduction of new technologies, new economies, or major competitors, which is a matter of concern ...
Message authentication with one-way hash functions (1992)

Fast message integrity and authentication services are much desired in today's high-speed network protocols. Current message authentication techniques are mostly encryption-based which is undesirable for several reasons. In this brief paper, we introduce encryption-free message authentication based entirely on fast one-way hash functions. Two methods are presented and their strength is analyzed. The security of the proposed methods is based on the strength of the underlying one-way hash function.
An Extremely Powerful Acylation Reaction of Alcohols with Acid Anhydrides Catalyzed by Trimethylsilyl Trifluoromethanesulfonate (1998)

Trimethylsilyl trifluoromethanesulfonate is an excellent catalyst for the acylation of alcohols with acid anhydrides. Highly functionalized primary, secondary, tertiary, and allylic alcohols, and phenols, were acylated cleanly and efficiently and in a fraction of the time used under the standard DMAP conditions.
Efficient Heterogeneous Biocatalysts by Entrapment of Lipases in Hydrophobic Sol–Gel Materials (1995)

Alkyltrimethoxysilanes yield much better host matrices for lipases than tetramethoxysilane (see picture). This is revealed by the esterifications discussed herein catalyzed by lipases that are immobilized in RSi(OMe)3 gels. These heterogeneous biocatalysts are readily reusable and should also be suitable for continuous processes.
Genetic Defects in Vitamin A Metabolism of the Retinal Pigment Epithelium (2003)

The metabolism of vitamin A and cycling of retinoids between the retinal pigment epithelium (RPE) and the neural retina is a complex process involving a specialized enzymes and proteins. Mutations in a number of the corresponding genes are responsible for various forms of inherited retinal dystrophy and dysfunction. Research into the causes and treatment of retinal diseases resulting from defects in vitamin A metabolism is currently the subject of intense interest, since disorders affecting RPE function are, in principle, more accessible to therapeutic intervention than those affecting the proteins of the photoreceptor cells. In this chapter we present an overview of the visual cycle, as well as the function of the known RPE genes involved in the conversion of vitamin A (all-trans retinol) to 11-cis retinal, the chromophore of the visual pigments. We describe the identification of disease-associated mutations in this set of genes in patients with diverse forms of retinal dystrophy and dysfunction, as well as the spectrum of mutations and associated phenotypes. We also discuss the results of recent studies using animal models of the disease caused by mutations of RPE65. On the basis of these advances, it is hoped that patients with defects in RPE vitamin A metabolism will be among the first successfully treated by targeted therapies likely to become available in the near future.
Expression of the FGFR1 gene in human breast‐carcinoma cells (1994)

Fibroblast growth factors (FGF) constitute a family of at least 9 members which act through high-affinity tyrosine-kinase receptors encoded by 4 distinct genes. In humans, the FGFR1 gene is located in chromosomal region 8p12. Its amplification and expression were examined in a panel of 110 breast carcinoma samples by Southern- and Northern-blot analyses. FGFR1 was amplified in 9% and overexpressed in about 15% of the tumors studied. In situ hybridization experiments were performed on tissue sections of normal breast and tumors with a high level of FGFR1 expression. In both normal and tumoral tissues, FGFR1 RNA was detected in the epithelial cells. Overexpression of FGFR1 seems to be associated with small, well-differentiated diploid tumors.
The Science and Practice of Bone Health in Oncology: Managing Bone Loss and Metastasis in Patients With Solid Tumors (2009)

Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.
Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial (2017)

National Cancer Institute and Merck KGaA.
Vitamin D: a hormone for all seasons--how much is enough? (2005)

Further understanding of its endocrine mechanisms and increased evidence for autocrine/paracrine actions has recently enhanced our knowledge of the biological activities of the vitamin D metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D). The recognition of the contribution of vitamin D depletion to increased risk of osteoporosis, and most importantly the risk of hip fracture in the elderly, has increased the clinical significance of clinical laboratory testing for vitamin D status. Research has revealed that at least three genes contribute to vitamin D activity within tissues. These are the vitamin D receptor as well as two major vitamin D metabolising enzymes, CYP27B1, responsible for synthesis of 1,25(OH)2D and CYP24, responsible for catabolism of vitamin D metabolites. Current research focuses on the contribution of vitamin D metabolism to increasing vitamin D activity. This is of particular interest in bone forming cells where increased 1,25(OH)2D activity has been proposed to contribute to strengthening the skeleton. As well, solid tumours such as prostate, breast and colon cancers are another increasing area of vitamin D research. The major issues for the clinical laboratory in vitamin D testing include defining clinical decision limits for the interpretation of serum 25-hydroxyvitamin D (25OHD) levels and improving the precision and accuracy of this assay.
An Auction-Based Multiple Constraints Task Allocation Algorithm for Multi-UAV System (2016)

Task allocation is a very important part in multi-UAV system. There are a lot of factors needed to be taken into consideration when assigning a dynamic task to one of the UAV in the multi-UAV system. We aim at solving the multi-UAV dynamic task allocation problem under multiple constraints. In this paper, we propose a method which uses the auction algorithm to assign the dynamic tasks to the UAVs. We propose a multi-layer cost computation method, in which the computation of the cost is divided into four layers in accordance with the four types of constraints. In this way, we solve multiple constraints and provide a way of calculating the price for bid. We use a simulation experiment to show the effectiveness of the new method. The result indicates that our proposed method can assign the new tasks very well and solve the multiple constraints at the same time.
Tumor-Infiltrating Regulatory T Cells Inhibit Endogenous Cytotoxic T Cell Responses to Lung Adenocarcinoma (2013)

Immune cells comprise a substantial proportion of the tumor mass in human nonsmall cell lung cancers (NSCLC), but the precise composition and significance of this infiltration are unclear. In this study, we examined immune complexity of human NSCLC as well as NSCLC developing in CC10-TAg transgenic mice, and revealed that CD4(+) T lymphocytes represent the dominant population of CD45(+) immune cells, and, relative to normal lung tissue, CD4(+)Foxp3(+) regulatory T cells (Tregs) were significantly increased as a proportion of total CD4(+) cells. To assess the functional significance of increased Tregs, we evaluated CD8(+) T cell-deficient/CC10-TAg mice and revealed that CD8(+) T cells significantly controlled tumor growth with antitumor activity that was partially repressed by Tregs. However, whereas treatment with anti-CD25-depleting mAb as monotherapy preferentially depleted Tregs and improved CD8(+) T cell-mediated control of tumor progression during early tumor development, similar monotherapy was ineffective at later stages. Because mice bearing early NSCLC treated with anti-CD25 mAb exhibited increased tumor cell death associated with infiltration by CD8(+) T cells expressing elevated levels of granzyme A, granzyme B, perforin, and IFN-γ, we therefore evaluated carboplatin combination therapy resulting in a significantly extended survival beyond that observed with chemotherapy alone, indicating that Treg depletion in combination with cytotoxic therapy may be beneficial as a treatment strategy for advanced NSCLC.
Selective Charging of tRNA Isoacceptors Explains Patterns of Codon Usage (2003)

We modeled how the charged levels of different transfer RNAs (tRNAs) that carry the same amino acid (isoacceptors) respond when this amino acid becomes growth-limiting. The charged levels will approach zero for some isoacceptors (such as tRNA2Leu) and remain high for others (such as tRNA4Leu), as determined by the concentrations of isoacceptors and how often their codons occur in protein synthesis. The theory accounts for (synonymous) codons for the same amino acid that are used in ribosome-mediated transcriptional attenuation, the choices of synonymous codons in trans-translating transfermessenger RNA, and the overrepresentation of rare codons in messenger RNAs for amino acid biosynthetic enzymes.
Antisense oligonucleotide targeting TNF‐α can suppress co‐cr‐mo particle‐induced osteolysis (2008)

The most common cause of implant failure in joint replacement is aseptic loosening due to particle-induced osteolysis. TNF-alpha has been shown to be one of the key factors in the process of osteoclastogenesis. Anti-TNF agents are useful in the treatment of joint inflammation related to osteolysis. This study investigated the effect of a single subcutaneous dose of an antisense oligonucleotide (ASO) on particle-induced osteolysis. We utilized the murine calvaria osteolysis model in C57BL/J6 mice. Bone resorption was measured by the toluidine blue staining. Osteoclasts were detected by tartrate resistant acid phosphatase (TRAP) staining assay and were quantified by a TRAP quantification kit. Results show that bone resorption is 0.347 +/- 0.09 mm(2) in mice with particle implantation, and decreased to 0.123 +/- 0.05 mm(2) and 0.052 +/- 0.02 mm(2) after ASO treatment with low and high doses, respectively. The number of osteoclasts in animal calvaria treated with ASO is reduced compared with that of untreated animals, and the quantification results indicate that about 90% of osteoclastogenesis is suppressed by the ASO. In addition, the osteoclastogenesis can be reestablished by the addition of TNF-alpha. In conclusion, we demonstrate that the antisense oligonucleotide targeting to TNF-alpha can suppress osteolysis induced by metal particles in a murine calvaria model. This new finding may be of value in the search for novel therapeutic methods for implant loosening.
Activation of Interferon Regulatory Factor 3 Is Inhibited by the Influenza A Virus NS1 Protein (2000)

We present a novel mechanism by which viruses may inhibit the alpha/beta interferon (IFN-alpha/beta) cascade. The double-stranded RNA (dsRNA) binding protein NS1 of influenza virus is shown to prevent the potent antiviral interferon response by inhibiting the activation of interferon regulatory factor 3 (IRF-3), a key regulator of IFN-alpha/beta gene expression. IRF-3 activation and, as a consequence, IFN-beta mRNA induction are inhibited in wild-type (PR8) influenza virus-infected cells but not in cells infected with an isogenic virus lacking the NS1 gene (delNS1 virus). Furthermore, NS1 is shown to be a general inhibitor of the interferon signaling pathway. Inhibition of IRF-3 activation can be achieved by the expression of wild-type NS1 in trans, not only in delNS1 virus-infected cells but also in cells infected with a heterologous RNA virus (Newcastle disease virus). We propose that inhibition of IRF-3 activation by a dsRNA binding protein significantly contributes to the virulence of influenza A viruses and possibly to that of other viruses.
A novel class of human type I interferons (1985)

The screening of a cDNA library prepared from mRNA of Sendai virus induced Namalwa (human Burkitt's lymphoma) cells, using a human IFN-alpha 2 DNA probe under conditions of low stringency, identified two weakly hybridizing clones containing sequences related to, but discernably different from those of the IFN-alpha class. Sequence and hybridization analysis of these cDNAs as well as expression in E. coli provided evidence that they encode proteins which have the characteristics of IFN type I but which are sufficiently diverged in sequence from both IFN-alpha s and IFN-beta to suggest that they are representatives of a new and distinct class of interferons named interferon-omega. Hybridization of these sequences to genomic DNA reveals that this class contains at least four members.
Comparison of full‐field digital mammography to screen‐film mammography with respect to contrast and spatial resolution in tissue equivalent breast phantoms (2005)

To determine if the improved contrast resolution of full-field digital mammography (FFDM) with reduced spatial resolution allows for superior or equal phantom object detection compared with screen-film mammography (SFM). Tissue equivalent breast phantoms simulating an adipose to glandular ratio of 50/50,30/70, and 20/80 were imaged according to each manufacturers' recommendation with four full-field digital mammography units (Fuji, Sectra, Fischer, and General Electric) and a screen-film mammography unit (MammoMatII 2000, Siemens, Munich, Germany). A total of 20 images were obtained in both hard- and soft-copy formats. For the purpose of soft-copy display, the screen-film hard-copy images were digitized with a 50 microm micron scanner. Six radiologists, experts in breast imaging, and three physicists, experts in scoring mammography phantoms, participated in a reader study where each reader scored each phantom for visibility of line-pairs and for 24 objects (fibers, clusters of specks, and masses). The data were recorded, entered into a database, and analyzed by a mixed-effect model. The limiting spatial resolution in line-pairs per millimeter visible with the digital units was less, regardless of display modality used, than that provided by the screen-film unit. The difference was statistically significant for the General Electric (p < 0.01) and Fuji digital mammography units (p = 0.03). With respect to the number of visible objects, a statistically significant higher number could be detected with the screen-film unit as compared to the Fischer (p < 0.01) and Sectra (p < 0.01) digital mammography units, but there was no significant difference between the other digital units and screen film. Overall, there was significantly better performance on the 50/50 phantom than with the 30/70 and 20/80 phantoms (p = 0.01, p < 0.01) for object visibility. For the digital mammography units, soft-copy display performed better than hard-copy display for the Fischer and Sectra images, but worse for Fuji and General Electric. In addition, soft-copy display of digitized screen-film images was significantly better than hard-copy display (p =0.02) of the original screen films for object visibility, but worse for spatial resolution. The higher contrast resolution of the FFDM units tested did not result in improved detection of line-pair resolution or objects in the phantoms tested versus screen-film mammography. The phantom performance of a digital mammography unit seems to be influenced by the type of detection task (line-pair resolution versus object visibility), the display modality (soft-copy versus hard-copy) chosen to score the phantoms, and the parenchymal pattern composition of the phantom.
Applying Map Databases to Advanced Navigation and Driver Assistance Systems (2001)

Navigation map databases have evolved during the last 10 years in coverage, content and accuracy to such a degree that they are being used (and considered) for applications beyond vehicle navigation. For a number of advanced driver assistance systems (ADAS) in Europe and North America, the navigation maps are being enhanced to offer new functions. This will complement dynamic route guidance, with location referencing, descriptions of delays, floating car data and re-routeing, all requiring developments in traffic management, road capacity balancing and routing algorithms.
Substrate Specificity of Human Nucleoside-diphosphate Kinase Revealed by Transient Kinetic Analysis (1998)

Nucleoside-diphosphate kinases (NDKs) catalyze the transfer of gamma-phosphoryl groups from NTPs via an active site histidine to NDPs using a ping-pong mechanism. We have used the change of intrinsic tryptophan fluorescence that occurs upon phosphorylation of NDK to measure the rates of phosphorylation and dephosphorylation with a range of nucleotides and nucleotide analogues. For natural nucleotides, the rates of phosphorylation and dephosphorylation were linearly dependent upon nucleotide concentration until they became too fast to measure. The second order rate constants for phosphorylation by natural NTPs varied between 0.7 and 13 x 10(6) M-1 s-1. Dephosphorylation by NDPs was 2-3-fold faster than the corresponding phosphorylation reaction, and dephosphorylation by dNDPs was 3-4-fold slower than the equivalent NDPs. In all cases, second order rate constants were highest for guanine followed by adenine and lowest for cytosine nucleotides. NDK also catalyzes the transfer of thiophosphate from adenosine 5'-O-(thiotriphosphate) (ATPgammaS) and guanosine 5'-O-(thiotriphosphate) (GTPgammaS) to NDP, but at (1)/(1000) of the equivalent phosphoryl transfer rates. In this case, the observed rate constants of phosphorylation and dephosphorylation were hyperbolically dependent on nucleotide concentration. Thiophosphorylation by ATPgammaS and GTPgammaS occurred with kmax of 2.8 and 1.35 s-1 and Kd of 145 and 36 muM respectively. For dethiophosphorylation by a range of NDPs, kmax was in the range of 5-30 s-1, whereas Kd varied between 0.16 and 3.3 mM. Guanine had the lowest Kd values, and cytosine had the highest. The data are consistent with fast reversible binding of the nucleotide followed by the rate-limiting phosphoryl transfer. Thiophosphates change only the rate of the phosphoryl transfer step, whereas both events are influenced by the base. Modification at the 2'-hydroxyl of ribose has only a small effect, while the overall rate of phosphoryl transfer is reduced 1000-fold by modification at the 3'-ribose.
Chelated Ruthenium Catalysts for Z-Selective Olefin Metathesis (2011)

We report the development of ruthenium-based metathesis catalysts with chelating N-heterocyclic carbene (NHC) ligands that catalyze highly Z-selective olefin metathesis. A very simple and convenient procedure for the synthesis of such catalysts has been developed. Intramolecular C-H bond activation of the NHC ligand, promoted by anion ligand substitution, forms the appropriate chelate for stereocontrolled olefin metathesis.
How best to provide mobile access to health documents (2012)

An international group wants your opinion of its guide for providing private health information to patients via smartphones and tablets. There's just one catch.
Pathogen-induced systemic activation of a plant defensin gene in Arabidopsis follows a salicylic acid-independent pathway. (1996)

A 5-kD plant defensin was purified from Arabidopsis leaves challenged with the fungus Alternaria brassicicola and shown to possess antifungal properties in vitro. The corresponding plant defensin gene was induced after treatment of leaves with methyl jasmonate or ethylene but not with salicylic acid or 2,6-dichloroisonicotinic acid. When challenged with A. brassicicola, the levels of the plant defensin protein and mRNA rose both in inoculated leaves and in nontreated leaves of inoculated plants (systemic leaves). These events coincided with an increase in the endogenous jasmonic acid content of both types of leaves. Systemic pathogen-induced expression of the plant defensin gene was unaffected in Arabidopsis transformants (nahG) or mutants (npr1 and cpr1) affected in the salicylic acid response but was strongly reduced in the Arabidopsis mutants eln2 and col1 that are blocked in their response to ethylene and methyl jasmonate, respectively. Our results indicate that systemic pathogen-induced expression of the plant defensin gene in Arabidopsis is independent of salicylic acid but requires components of the ethylene and jasmonic acid response.
Structural trends in central Britain from images of gravity and aeromagnetic fields (1990)

Digital image processing techniques have been used to analyse the regional gravity and aeromagnetic datasets in central Britain. Colour and shaded-relief images have been generated which convey information on both anomaly amplitude (as colour) and anomaly gradient (as relief) and highlight structural trends, lineaments and textural contrasts not easily discernible on standard contour maps. We have identified some of the more important features and have tried to relate these to the evolution of the crust in each region. On a broad scale the images emphasize Caledonoid (ENE) trends to the north of the Solway line and both Tornquist (SE) and Caledonoid (NE to ENE) trends to the south. The pattern of magnetic anomalies over central England seems to define the extent of the shallow late Precambrian–early Palaeozoic basement of the Midlands Microcraton and delineates crustal elements and characteristic trends within it. Magnetic lineaments and the grain of gravity anomalies, trending in northeasterly and northwesterly directions on either side of the microcraton, seem to relate to structures which originated during the evolution of the Welsh and eastern English Caledonides respectively. Where Lower Palaeozoic and Precambrian rocks form the concealed ‘basement’, as in most of England, the gravity lineaments tend to reflect the influence of basement fractures on the subsequent pattern of sedimentation whereas many of the features on the magnetic images are more directly related to structures within the basement itself.