gebhart/patrepeval huggingface dataset:
Instability in dynamic fracture (1991)

Cracks in brittle materials have terminal velocities far below theoretical predictions. To address this problem we have investigated the propagation of cracks in a brittle plastic (polymethylmethacrylate). Velocity measurements with resolution an order of magnitude better than past experiments reveal the existence of a critical velocity at which the velocity begins to oscillate, the mean acceleration drops sharply, and a pattern is formed on the fracture surface. Thus the dynamics of cracks may be governed by a dynamical instability.
Security for the digital library-protecting documents rather than channels (2002)

In this paper we focus on the mechanisms necessary to put a security architecture for digital libraries in place. This includes protection of the content, feasibility of payment and assertion of copy- and usage rights. While current research in secure Web technology (like SSH, SHTTP or SSL) focuses on the protection of the communication channel, proposals for protecting digital content usually rely on some sort of secure container to realize the functions mentioned above. We explain the concepts underlying both approaches using the IBM Cryprolope technology as an example for secure containers.
Regulation of the Expression of GARP/Latent TGF-β1 Complexes on Mouse T Cells and Their Role in Regulatory T Cell and Th17 Differentiation (2013)

GARP/LRRC32 was defined as a marker of activated human regulatory T cells (Tregs) that is responsible for surface localization of latent TGF-β1. We find that GARP and latent TGF-β1 are also found on mouse Tregs activated via TCR stimulation; however, in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL-2 or IL-4 exposure in the absence of TCR signaling. GARP is expressed at a low level on Tregs within the thymus, and Treg precursors from the thymus concomitantly express GARP and Foxp3 upon exposure to IL-2. The expression of GARP is independent of TGF-β1 and TGF-β1 loading into GARP and is independent of furin-mediated processing of pro-TGF-β1 to latent TGF-β1. Specific deletion of GARP in CD4(+) T cells results in lack of expression of latent TGF-β1 on activated Tregs. GARP-deficient Tregs develop normally, are present in normal numbers in peripheral tissues, and are fully competent suppressors of the activation of conventional T cells in vitro. Activated Tregs expressing GARP/latent TGF-β1 complexes are potent inducers of Th17 differentiation in the presence of exogenous IL-6 and inducers of Treg in the presence of IL-2. Induction of both Th17-producing cells and Tregs is caused preferentially by Tregs expressing the latent TGF-β1/GARP complex on their cell surface rather than by secreted latent TGF-β1.
Pleiotropic Enhancement of Bacterial Pathogenesis Resulting from the Constitutive Activation of theListeria monocytogenesRegulatory Factor PrfA (2005)

Listeria monocytogenes is a facultative intracellular bacterial pathogen that causes serious disease in immunocompromised individuals, pregnant women, and neonates. Bacterial virulence is mediated by the expression of specific gene products that facilitate entry into host cells and enable bacterial replication; the majority of these gene products are regulated by a transcriptional activator known as PrfA. L. monocytogenes strains containing prfA E77K or prfA G155S mutations exhibit increased expression of virulence genes in broth culture and are hypervirulent in mice. To define the scope of the influences of the prfA E77K and prfA G155S mutations on L. monocytogenes pathogenesis, multiple aspects of bacterial invasion and intracellular growth were examined. Enhanced bacterial invasion of host epithelial cells was dependent on the expression of a number of surface proteins previously associated with invasion, including InlA, InlB, and ActA. In addition to these surface proteins, increased production of the hly-encoded secreted hemolysin listeriolysin O (LLO) was also found to significantly enhance bacterial invasion into epithelial cell lines for both prfA mutant strains. Although prfA E77K and prfA G155S strains were similar in their invasive phenotypes, the infection of epithelial cells with prfA E77K strains resulted in host cell plasma membrane damage, whereas prfA G155S strains did not alter plasma membrane integrity. Bacterial infection of human epithelial cells, in which the production of LLO is not required for bacterial entry into the cytosol, indicated that prfA E77K cytotoxic effects were mediated via LLO. Both prfA E77K and prfA G155S strains were more efficient than wild-type bacteria in gaining access to the host cell cytosol and in initiating the polymerization of host cell actin, and both were capable of mediating LLO-independent lysis of host cell vacuoles in cell lines for which L. monocytogenes vacuole disruption normally requires LLO activity. These experiments illuminate the diverse facets of L. monocytogenes pathogenesis that are significantly enhanced by the constitutive activation of PrfA via prfA mutations and underscore the critical role of this protein in promoting L. monocytogenes virulence.
ON THE REPRESENTATION OF OPERATORS IN BASES OF (1992)

This paper describes exact and explicit representations of the differential operators, dn/dXn, n = 1,2,.--, in orthonormal bases of compactly supported wavelets as well as the rep- resentations of the Hilbert transform and fractional derivatives. The method of computing these representations is directly applicable to multidimensional convolution operators. Also, sparse representations of shift operators in orthonormal bases of compactly supported wavelets are discussed and a fast algorithm requiring O(N log N) operations for computing the wavelet coefficients of all N circulant shifts of a vector of the length N = 2n is constructed. As an example of an application of this algorithm, it is shown that the storage requirements of the fast algorithm for applying the standard form of a pseudodifferential operator to a vector (see (G. Beylkin, R. R. Coifman, and V. Rokhlin, Comm. Pure. Appl. Math., 44 (1991), pp. 141-183)) may be reduced from O(N) to O(log2 N) significant entries. The computation of the nonstandard forms of many other operators reduces to solving a simple system of linear algebraic equations. Among such operators are fractional derivatives, Hilbert and Riesz transforms, and other operators for which analytic expressions are available. For convolution operators, there are significant simplifications in computing the nonstandard form since the vanishing moments of the autocorrelation function of the scaling function simplify the quadrature formu- las. Moreover, by solving a system of linear algebraic equations combined with the asymptotics of wavelet coefficients, we arrive at an effective method for computing the nonstandard form of convolution operators. As examples, we compute the nonstan- dard forms of the Hilbert transform and fractional derivatives. The generalization of this method for multidimensional convolution operators is straightforward.
Monoclonal Antibodies to Fibroblast Growth Factor Receptor 2 Effectively Inhibit Growth of Gastric Tumor Xenografts (2010)

Anti-FGFR2 mAbs GAL-FR21 and GAL-FR22 have potential for the treatment of gastric and other tumors.
Functional Abnormalities in Isolated Arteries from Goto-Kakizaki and Streptozotocin-treated Diabetic Rat Models (2005)

Several different rat models have been developed for both type 1 and type 2 diabetes with the aim of displaying specific traits of diabetes. For example, a review on nephropathy associated with type 2 diabetes included 16 different rodent models ; new models are still being developed. The large number of different models developed for different traits makes it difficult to choose the right model for a given study. It is often a problem that the models are not sufficiently characterized, which makes it easy to misinterpret data or even come to the wrong conclusions. In this brief review, we will concentrate on the functional responses obtained in vitro from mesenteric arteries and aortic segments from rat models of diabetes. Since it is beyond the scope of this review to overview all different rodent models of diabetes, we will focus on two commonly used models of diabetes, namely the streptozotocin (STZ)-induced type 1 diabetic rat model and the inbred type 2 diabetic Goto-Kakizaki (GK)-rat model.
Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis (2010)

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (∼1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.
Motivational predictors of weight loss and weight-loss maintenance. (1996)

Self-determination theory proposes that behavior change will occur and persist if it is autonomously motivated. Autonomous motivation for a behavior is theorized to be a function both of individual differences in the autonomy orientation from the General Causality Orientations Scale and of the degree of autonomy supportiveness of relevant social contexts. We tested the theory with 128 patients in a 6-month, very-low-calorie weight-loss program with a 23-month follow-up. Analyses confirmed the predictions that (a) participants whose motivation for weight loss was more autonomous would attend the program more regularly, lose more weight during the program, and evidence greater maintained weight loss at follow-up, and (b) participants' autonomous motivation for weight loss would be predicted both by their autonomy orientation and by the perceived autonomy supportiveness of the interpersonal climate created by the health-care staff.
MinDE-Dependent Pole-to-Pole Oscillation of Division Inhibitor MinC in Escherichia coli (1999)

By inhibiting FtsZ ring formation near the cell ends, the MinC protein plays a critical role in proper positioning of the division apparatus in Escherichia coli. MinC activity requires that of MinD, and the MinE peptide provides topological specificity by suppressing MinC-MinD-mediated division inhibition specifically at the middle of the cell. We recently presented evidence that MinE not only accumulates in an FtsZ-independent ring structure at the cell's middle but also imposes a unique dynamic localization pattern upon MinD in which the latter accumulates alternately in either one of the cell halves in what appears to be a rapidly oscillating membrane association-dissociation cycle. Here we show that functional green fluorescent protein-MinC displays a very similar oscillatory behavior which is dependent on both MinD and MinE and independent of FtsZ. The results support a model in which MinD recruits MinC to its site of action and in which FtsZ ring assembly at each of the cell ends is blocked in an intermittent and alternate fashion.
Benzylisoquinoline Alkaloid Metabolism: A Century of Discovery and a Brave New World (2013)

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant specialized metabolites with a long history of investigation. Although the ecophysiological functions of most BIAs are unknown, the medicinal properties of many compounds have been exploited for centuries. These include the narcotic analgesics codeine and morphine, the antimicrobial agents sanguinarine and berberine, and the antitussive and anticancer drug noscapine. BIA biosynthesis involves a restricted number of enzyme types that catalyze landmark coupling reactions and subsequent functional group modifications. A pathogenesis-related (PR)10/Bet v1 'Pictet-Spenglerase', several O-methyl-, N-methyl- and O-acetyltransferases, cytochromes P450, FAD-dependent oxidases, non-heme dioxygenases and NADPH-dependent reductases have been implicated in the multistep pathways leading to structurally diverse alkaloids. A small number of plant species, including opium poppy (Papaver somniferum) and other members of the Ranunculales, have emerged as model systems to study BIA metabolism. The expansion of resources to include a wider range of plant species is creating an opportunity to investigate previously uncharacterized BIA pathways. Contemporary knowledge of BIA metabolism reflects over a century of research coupled with the development of key innovations such as radioactive tracing, enzyme isolation and molecular cloning, and functional genomics approaches such as virus-induced gene silencing. Recently, the emergence of transcriptomics, proteomics and metabolomics has expedited the discovery of new BIA biosynthetic genes. The growing repository of BIA biosynthetic genes is providing the parts required to apply emerging synthetic biology platforms to the development of production systems in microbes as an alternative to plants as a commecial source of valuable BIAs.
Remodeling the pyramid--a concept whose time has come. (1989)

It is clear that the traditional treatment program, as illustrated by the pyramid, does not suppress inflammation in most patients with RA to an extent sufficient to prevent joint damage. There is no basis for the concept that slow acting drugs are uniquely disease modifying. Disease modification correlates best with control of inflammation. Contrary to popular wisdom, this has been best demonstrated with prednisone. The arbitrary concept of a drug being either antiinflammatory or disease modifying serves no useful purpose and should be dropped. Many medications provide incomplete or temporary suppression of inflammation, presumably by differing mechanisms of action. Based on this rationale, a therapeutic program is proposed, employing a combination of drugs to control inflammation in the critical early stages of RA. With this step-down bridge concept, medications are sequentially withdrawn in contrast to the traditional pyramid, in which they have been sequentially added. Our early experience with patients indicates that toxicity is no greater problem with combined drugs than with the same drugs used individually. Time and comparative observations will be needed to show the optimum combination of drugs and whether the step-down bridge concept will achieve the sought-for and presently unobtained goal of early and sustained control of inflammation, improved quality of life, and prevention of bone and joint damage.
Demonstration by Two-Color Flow Cytometry That Tyrosine Kinase Activity Is Required for Down-Modulation of the Oncogenic neu Receptor (1994)

Expression of rat oncogenic neu receptor, p185T-neu (a growth factor receptor with constitutive tyrosine kinase activity), causes cells to become transformed. Treatment with anti-neu receptor monoclonal antibodies reverts the transformed phenotype by down-modulation of p185T-neu. Monoclonal antibody treatment of cells expressing normal neu receptor, p185C-neu (which lacks constitutive tyrosine kinase activity), does not result in down-modulation of p185C-neu. To understand further the role the biochemical activity of p185T-neu plays in transformation and endocytosis, we created a series of mutations in p185T-neu. We found that fibroblasts expressing the tyrosine kinase-defective mutants cannot form foci in culture, colonies in soft agar, or tumors in immunocompromised mice. To follow the antibody-induced endocytosis of neu receptors expressed in these transfectants, we developed a novel two-color flow cytometric assay and confirmed receptor localization by electron microscopy. Cells were treated with mAb7.16.4 over time. After 4 hr of antibody treatment, less than 50% of full-length p185T-neu and of mutant T691 remained on the cell surface, whereas internal expression of the neu receptors within these cells initially increased and then decreased to the original internal receptor level. In contrast, the level of kinase-deficient mutated neu receptors remaining on the cell surface initially decreased by 35%, but, after 4 hr of antibody treatment, the cell surface expression level returned to approximately the original level. Concurrently, fluctuations in expression levels were seen internally over time as well. These cell lines were also treated with gold-conjugated mAb7.16.4. Using electron microscopy, we consistently found the gold particles within multivesicular bodies of cell lines expressing full-length or mutated neu receptor. These data strongly suggest that the fate of the neu receptor, once internalized, is directed by its tyrosine kinase activity. When the kinase activity of the neu receptor is disrupted, the receptor is internalized but recycled to the cell surface, whereas neu receptors which have constitutive kinase activity are internalized and presumably degraded when engaged with anti-neu receptor mAb. Understanding the regulation of receptor endocytosis, degradation, and recycling will contribute to the development of novel therapeutic protocols to combat human malignancies, particularly those associated with the overexpression of the human homologue of the neu receptor, c-erbB2.
Present and future pharmacotherapy for osteoporosis (2003)

Although neither calcium nor vitamin D has been shown to prevent osteoporosis in postmenopausal women alone, the combination does. Both calcium and vitamin D are commonly used in the treatment of osteoporosis. The estrogens and raloxifene both prevent bone loss in postmenopausal women, and the estrogens probably also decrease the risk of first fracture. There is good evidence that raloxifene prevents further fractures in postmenopausal women who have already had fractures and some evidence that estrogen does as well. Calcitonin increases bone mineral density in early postmenopausal women and men with idiopathic osteoporosis, and also reduces the risk of new fractures in osteoporotic women. The bisphosphonate alendronate prevents bone loss and reduces fractures in healthy and osteoporotic postmenopausal women, and in osteoporotic men. Risedronate is more potent and has fewer upper gastrointestinal side effects than alendronate, and reduces the incidence of fractures in osteoporotic women. Intermittent use of the potent bisphosphonate zoledronate also increases bone mineral density and may become an alternative in the prevention and treatment of osteoporosis. All of the agents discussed above prevent bone resorption, whereas teriparatide increases bone formation and is effective in the treatment of osteoporotic women and men. In the treatment of secondary osteoporosis associated with the use of glucocorticoids to treat inflammation or prevent rejection after transplantation, the bisphosphonates are effective. The agents that have undergone some clinical trialing as new or alternative drugs for the treatment of osteoporosis include tibolone, new SERMs, androgens, growth hormone, insulin-like growth factor-1 and stontium ranelate. The targets/drugs that are being developed to inhibit bone resorption include the OPG/ RANKL/RANK system, cathepsin K inhibitors, vitronectin receptor antagonists, estren, the interleukin-6 and gp130 system, cytokines and growth factors. New drugs/targets to promote bone formation include the commonly used lipid-lowering statins and the calcilytic release of PTH.
Radar Waveform Selection-A Simplified Approach (1971)

Radar measurement and resolution performance, as well as target detection in clutter, depend largely on the transmitted waveform. This explains the sizable effort that has gone into studies of radar waveforms, including attempts at the synthesis of optimum waveforms. This paper shows that, despite the unlimited variety of radar signals, waveform selection is a straightforward process. There are only four classes of waveforms, each with distinct resolution properties. When the target environment is analyzed for a particular application, it is rather evident which of these classes will fit the situation best. Choice of the specific waveform within the selected class then is merely a matter of practical implementation. Although the facts used in developing the unified theory of this paper are not new, it is demonstrated that these facts can be combined into an extremely simple theory of waveform design. Much of today's work is guided by past approaches to a particular problem, and when a design is completed there may be a question as to how close to the optimum it is. The theory presented here permits a systematic approach to waveform selection, with the important benefit that the designer knows exactly where and how much he may have deviated from the best design, and why this was done.
New Circulating-Water Devices Warm More Quickly than Forced-Air in Volunteers (2007)

The warming rate with the Kimberly Clark system was 25% faster than with the Allon system and twice as fast as with the Bair Hugger. Both circulating-water systems thus warmed hypothermic volunteers in significantly less time than the forced-air system.
Synthesis of the CC-chemokines MIP-1alpha, MIP-1beta, and RANTES is associated with a type 1 immune response (1996)

Lymphocytes regulate the immune response by secreting cytokines that control the activity and function of effector cells. Chemokine subsets are ideal candidates for recruitment of specific effector cells to inflammatory sites or to other lesions because of their selective chemoattractant activities. Given the Th1-Th2 model of immune regulation and the particular role of leukocyte recruitment for the outcome of the response, we analyzed whether a subset of human chemokines is associated with a specific type of immune response. Therefore, we have analyzed the human T cell response to Ags prepared from Yersinia enterocolitica and Ascaris suum with respect to cytokine mRNA-synthesis and secretion. For the Gram-negative bacterium Y. enterocolitica, induction of a type 1 response is indicated by IL-2 and IFN-gamma production, and for the nematode A. suum, a type 2 response is based on IL-4 and IL-5 production. Interestingly, expression of three CC-chemokines (i.e., MIP-1alpha, MIP-1beta, and RANTES) correlated with the type 1 response induced by Y. enterocolitica Ag. Chemokine secretion is not restricted to T lymphocytes; therefore, synthesis of MIP-1alpha, MIP-1beta, and RANTES was also characterized in human T cell clones that display a cytokine pattern indicative of the Th2, Th0, or Th1 phenotype. Again CC-chemokine secretion correlated with the Th1-like phenotype. In six analyzed IL-2- and IFN-gamma- secreting Th1 clones and in two Th0 clones, MIP-1alpha, MIP-1beta, and RANTES were detected, while none or only minimal secretion of these CC-chemokines was observed in three IL-4- and IL-5-producing Th2 cell clones.