gebhart/patrepeval huggingface dataset:
Routing to support communication in dependable networks (2002)

We can observe the exploding use of the Internet for various applications, ranging from ordinary E-mail exchange and all kinds of net-oriented databases, to large distributed cooperative projects. All these emerging activities heavily rely on the continuous availability of the Internet services, with regard to their proper function as well as to their timely execution. Therefore, it is felt to be extremely necessary to make especially the entire communication within the system as robust as possible. We discuss these dependability problems in detail and present a survey of research approaches to deal with them. Thereby, the focus of attention is the discussion of routing, ie, the propagation of information between non-adjacent nodes, at three levels of the Web communication: in local networks connected to server nodes, in the server machines, and in the "network of networks" itself.
Activation of the Contact System of Coagulation by a Monoclonal Antibody Directed Against a Neodeterminant in the Heavy Chain Region of Human Coagulation Factor XII (Hageman Factor) (1989)

We studied the characteristics of two monoclonal antibodies (mAbs), F1 and F3, against human coagulation factor XII (Hageman factor). Experiments with trypsin-digested 125I-factor XII revealed that the epitope for mAb F1 is located in the NH2-terminal Mr 40,100 portion of factor XII, whereas that for mAb F3 resides in the COOH-terminal Mr 30,000 portion of this protein. Factor XII in fresh plasma (single-chain factor XII) bound approximately 190 times less to mAb F1 than factor XII in dextran sulfate-activated plasma (cleaved factor XII). However, no difference in accessibility of the epitope for mAb F1 was observed between cleaved and single-chain factor XII when bound to glass. mAb F3 appeared to bind to both single-chain and cleaved factor XII in plasma as well as when bound to glass. Neither mAb F1, nor F3 affected the amidolytic activity of factor XIIa, whereas both mAb F1 and F3 inhibited factor XII-coagulant activity to about 15 and 70%, respectively, at a molar ratio of mAb to factor XII of 20 to 1. mAb F1, as well as F(ab')2 and F(ab') fragments of this antibody induced activation of the contact system in plasma, as reflected by the generation of factor XIIa. C1 inhibitor and kallikrein. C1 inhibitor complexes. Activation was induced neither upon incubation with mAb F3, nor with that of control mAbs. mAb F1-induced contact activation required the presence of factor XII, prekallikrein, and high molecular weight kininogen and, in contrast to activation by negatively charged surfaces, was not inhibited by the presence of Polybrene. Based on these results we propose that a conformational change in factor XII is a key event in the activation process of this molecule. This conformational change can be induced by binding of factor XII to a surface as well as by proteolytic cleavage. As mAb F1 can also induce this conformational change, this antibody may provide a unique tool in studies of the activation of factor XII.
Molecular Pathways: MERTK Signaling in Cancer (2013)

MERTK is a receptor tyrosine kinase of the TAM (Tyro3, Axl, MERTK) family, with a defined spectrum of normal expression. However, MERTK is overexpressed or ectopically expressed in a wide variety of cancers, including leukemia, non-small cell lung cancer, glioblastoma, melanoma, prostate cancer, breast cancer, colon cancer, gastric cancer, pituitary adenomas, and rhabdomyosarcomas, potentially resulting in the activation of several canonical oncogenic signaling pathways. These include the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways, as well as regulation of signal transducer and activator of transcription family members, migration-associated proteins including the focal adhesion kinase and myosin light chain 2, and prosurvival proteins such as survivin and Bcl-2. Each has been implicated in MERTK physiologic and oncogenic functions. In neoplastic cells, these signaling events result in functional phenotypes such as decreased apoptosis, increased migration, chemoresistance, increased colony formation, and increased tumor formation in murine models. Conversely, MERTK inhibition by genetic or pharmacologic means can reverse these pro-oncogenic phenotypes. Multiple therapeutic approaches to MERTK inhibition are currently in development, including ligand "traps", a monoclonal antibody, and small-molecule tyrosine kinase inhibitors.
The gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA carboxylase. (1992)

We report the molecular cloning and DNA sequence of the gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA carboxylase. The biotin carboxylase gene encodes a protein of 449 residues that is strikingly similar to amino-terminal segments of two biotin-dependent carboxylase proteins, yeast pyruvate carboxylase and the alpha-subunit of rat propionyl-CoA carboxylase. The deduced biotin carboxylase sequence contains a consensus ATP binding site and a cysteine-containing sequence preserved in all sequenced bicarbonate-dependent biotin carboxylases that may play a key catalytic role. The gene encoding the biotin carboxyl carrier protein (BCCP) subunit of acetyl-CoA carboxylase is located upstream of the biotin carboxylase gene and the two genes are cotranscribed. As previously reported by others, the BCCP sequence encoded a protein of 16,688 molecular mass. However, this value is much smaller than that (22,500 daltons) obtained by analysis of the protein. Amino-terminal amino acid sequencing of the purified BCCP protein confirmed the deduced amino acid sequence indicating that BCCP is a protein of atypical physical properties. Northern and primer extension analyses demonstrate that BCCP and biotin carboxylase are transcribed as a single mRNA species that contains an unusually long untranslated leader preceding the BCCP gene. We have also determined the mutational alteration in a previously isolated acetyl-CoA carboxylase (fabE) mutant and show the lesion maps within the BCCP gene and results in a BCCP species defective in acceptance of biotin. Translational fusions of the carboxyl-terminal 110 or 84 (but not 76) amino acids of BCCP to beta-galactosidase resulted in biotinated beta-galactosidase molecules and production of one such fusion was shown to result in derepression of the biotin biosynthetic operon.
Sensing Starvation: a Homoserine Lactone—Dependent Signaling Pathway in Escherichia coli (1994)

When nutrients become limiting, many bacteria differentiate and become resistant to environmental stresses. For Escherichia coli, this process is mediated by the sigma s subunit of RNA polymerase. Expression of sigma s was induced by homoserine lactone, a metabolite synthesized from intermediates in threonine biosynthesis. Homoserine lactone-dependent synthesis of sigma s was prevented by overexpression of a newly identified protein, RspA. The function of homoserine lactone derivatives in many cell density-dependent phenomena and the similarity of RspA to a Streptomyces ambofaciens protein suggest that synthesis of homoserine lactone may be a general signal of starvation.
Expression of human immunodeficiency virus antigens in an attenuated Salmonella typhi vector vaccine. (1994)

Human immunodeficiency virus is known to enter the host at parenteral and mucosal sites and consequently an effective vaccine should stimulate immunity at both routes of entry. One approach toward stimulating HIV-specific mucosal and systemic immunity is the use of candidate live oral Salmonella typhi vector vaccine, strain CVD 908, which has been shown to stimulate mucosal and systemic immunity in volunteers. Using recombinant DNA techniques we constructed an expression cassette which comprises the lpp promoter (Plpp) and sequences encoding recombinant gp120 (rgp120). When the Plpp-rgp120 expression cassette is integrated into the chromosome of CVD 908 in the delta aroC allele, high levels of recombinant gp120 expression are observed. It is likely that effective immunity against HIV in humans will require immunization with multiple HIV antigens. Hence, a second expression cassette encoding two additional HIV antigens with vaccine potential, p24 (a HIV-1 gag gene product) and Nef (a putative regulator of HIV-1 gene expression) has been constructed. We plan to integrate the p24-Nef-encoding expression cassette into the aroD locus in the chromosome of CVD 908 delta aroC::rgp120 in a stable manner to produce a CVD 908-HIV vector vaccine that expresses multiple HIV antigens.
Gonadal hormones and pathogenesis of occlusive arterial thrombosis (1978)

Arterial thrombus formation was induced in male and female Wistar rats (3 mo) by inserting a loop-shaped polyethylene cannula into the abdominal aorta. Thrombogenesis was also induced in mature male and female New Zealand rabbits by constriction of the femoral artery and injection of ellagic acid. The criteria for thrombus development in the cannulated rats were: incidence of thrombosis (IT), obstruction time (OT), and thrombus weight (TW). We observed a significant sex difference in all these criteria of thrombogenesis in both rats and rabbits. Pretreatment of either sex with Depo-testosterone shortened OT, increased TW about fivefold in males and threefold in females, and increased mortality rate (MR) more than fourfold in both sexes. Prolonged pretreatment with Depo-testosterone increased in all aspects of thrombogenesis. Depo-estradiol had marginal ameliorating effects in male rats only. Both the antiandrogen Flutamide, and aspirin, significantly decreased the thrombogenic effects of testosterone. Thus, testosterone may be a significant risk factor in experimentally induced thrombogenesis in rats and rabbits.
Effect of wheat germ agglutinin on the viscoelastic properties of erythrocyte membrane. (1982)

The elasticity and viscosity of the human erythrocyte membrane were measured as a function of the concentration of wheat germ agglutinin (WGA) in a suspending solution containing 1 mg/ml albumin, approximately 5 X 10(5) cells/ml and between 0.0 and 0.2 microgram/ml WGA. Membrane elasticity was characterized by the elastic shear modulus, which provided a measure of the resistance of the membrane to constant-area elastic deformations that occurred in the membrane plane. The elastic shear modulus was determined by aspirating a portion of the membrane into a micropipette and measuring the extension of the membrane into the pipette as a function of the suction pressure. The results indicated no significant change in shear modulus for concentrations of WGA between 0.0 and 0.2 microgram/ml. Membrane viscosity was characterized by the coefficient of surface viscosity, which, in effect, was a measure of the membrane's resistance to rates of deformation. This coefficient was determined from the time required for an erythrocyte to recover its undeformed shape after it had been elongated by the application of an equal and opposite force applied at diametrically opposite points on the erythrocyte rim. The value for the coefficient of surface viscosity was found to increase by a factor of almost three when the WGA concentration was increased from 0.0 to 0.2 microgram/ml. These results indicated that, in the presence of albumin, WGA can increase membrane dissipation (viscosity) without altering the structural rigidity (elasticity) of the membrane.
A fundamental limit on delay estimation using partially correlated speckle signals (1995)

Delay estimation is used in ultrasonic imaging to estimate blood or soft tissue motion, to measure echo arrival time differences for phase aberration correction, and to estimate displacement for tissue elasticity measurements. In each of these applications delay estimation is performed using speckle signals which are at least partially decorrelated relative to one another. Delay estimates which utilize such data are subject to large errors known as false peaks and smaller magnitude errors known as jitter. While false peaks can sometimes be removed through nonlinear processing, jitter errors place a fundamental limit on the performance of delay estimation techniques. The authors apply the Cramer-Rao Lower Bound to derive an analytical expression which predicts the magnitude of jitter errors incurred when estimating delays using radio frequency (RF) data from speckle targets. The analytical expression presented includes the effects of signal decorrelation due to physical processes, corruption by electronic noise, and a number of other factors. Simulation results are presented which show that the performance of the normalized cross correlation algorithm closely matches theoretical predictions. These results indicate that for poor signal to noise ratios (0 dB) a small improvement in signal to noise ratio can dramatically reduce jitter magnitude. At high signal to noise ratios (30 dB) small amounts of signal decorrelation can significantly increase the magnitude of jitter errors.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Convergence of Progesterone and Epidermal Growth Factor Signaling in Breast Cancer (1998)

During late stages of breast cancer progression, tumors frequently acquire steroid hormone resistance with concurrent amplification of growth factor receptors; this alteration predicts a poor prognosis. We show here that following treatment with the progestin, R5020, breast cancer cells undergo a "biochemical shift" in the regulation of epidermal growth factor (EGF)-stimulated signaling pathways: R5020 potentiates the effects of EGF by up-regulating EGFR, c-ErbB2 and c-ErbB3 receptors, and by enhancing EGF-stimulated tyrosine phosphorylation of signaling molecules known to associate with activated type I receptors. Independently of EGF, R5020 increases Stat5 protein levels, association of Stat5 with phosphotyrosine-containing proteins, and tyrosine phosphorylation of JAK2 and Shc. Furthermore, progestins "prime" breast cancer cells for growth signals by potentiating EGF-stimulated p42/p44 mitogen-activated protein kinase (MAPK), p38 MAP kinase, and JNK activities. Although the levels of cyclin D1, cyclin E, and p21(WAF1), are up-regulated by R5020 alone, they are synergistically up-regulated by EGF in the presence of R5020. Up-regulation of cell cycle proteins by EGF is blocked by inhibition of p42/p44 MAPK only in the presence of R5020, supporting a shift in the regulation of these cell cycle mediators from MAPK-independent to MAPK-dependent pathways. In summary, progesterone selectively increases the sensitivity of key kinase cascades to growth factors, thereby priming cells for stimulation by latent growth signals. These data support a model in which breast cancer cell growth switches from steroid hormone to growth factor dependence.
Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming (2016)

The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.
Galectin-3 Cleavage: A Novel Surrogate Marker for Matrix Metalloproteinase Activity in Growing Breast Cancers (2007)

Failed therapies directed against matrix metalloproteinases (MMP) in cancer patients may be attributed, in part, to lack of diagnostic tools to differentiate between pro-MMPs and active MMPs, which indicate whether a treatment is efficacious or not. Because galectin-3 is cleavable in vitro by MMPs, we have developed differential antibodies recognizing its cleaved and noncleaved forms and tested their clinical utilization as a surrogate diagnostic marker for the presence of active MMPs in growing breast cancers. Wild-type and cleavage-resistant galectin-3 were constructed and expressed in galectin-3-null human breast carcinoma cells (BT-549). Tumorigenic and angiogenic potential of the clones was studied by injections into nude mice. MMP-2, MMP-9, full-length, and cleaved galectin-3 were localized in the xenografts by immunohistochemical analysis of paraffin-embedded sections using specific antibodies. Activities of MMP-2/9 were corroborated by in situ zymography on frozen tissue sections. Galectin-3 cleavage was shown in vivo by differential antibody staining and colocalized with predicted active MMPs both in mouse xenografts and human breast cancer specimens. In situ zymography validated these results. In addition, BT-549 cells harboring noncleavable galectin-3 showed reduced tumor growth and angiogenesis compared with the wild-type. We conclude that galectin-3 cleavage is an active process during tumor progression and could be used as a simple, rapid, and reliable surrogate marker for the activities of MMPs in growing breast cancers.
Caspase cleavage of Bim EL triggers a positive feedback amplification of apoptotic signaling (2004)

Members of the Bcl-2 protein family that share only the Bcl-2 homology 3 (BH3) domain are known mostly as sentinels for apoptotic stimuli and initiators of apoptosis. One BH3-only protein, Bim, is the major physiological antagonist of the prosurvival proteins in B and T lymphocytes. It is required for hematopoietic homeostasis and to preclude autoimmunity. Here, we show that the Bim EL isoform, which was predominant in T cells, existed in both phosphorylated and unphosphorylated forms. Whereas the unphosphorylated Bim EL was sequestered to microtubules by means of a direct interaction with tubulin, the phosphorylated protein was released from microtubules. The freed Bim EL was subjected to caspase cleavage at an early stage of apoptosis induced by stimuli that activate either the mitochondria- or death receptor-dependent apoptosis pathway. The N-terminally cleaved Bim EL became hyperactive in inducing apoptosis because of its more efficient targeting of Bcl-2. Thus, unlike many other BH3-only proteins, Bim EL can be activated downstream of the caspase cascade, leading to a positive feedback amplification of apoptotic signals.
Understanding the network-level behavior of spammers (2006)

This paper studies the network-level behavior of spammers, including: IP address ranges that send the most spam, common spamming modes (e.g., BGP route hijacking, bots), how persistent across time each spamming host is, and characteristics of spamming botnets. We try to answer these questions by analyzing a 17-month trace of over 10 million spam messages collected at an Internet "spam sinkhole", and by correlating this data with the results of IP-based blacklist lookups, passive TCP fingerprinting information, routing information, and botnet "command and control" traces.We find that most spam is being sent from a few regions of IP address space, and that spammers appear to be using transient "bots" that send only a few pieces of email over very short periods of time. Finally, a small, yet non-negligible, amount of spam is received from IP addresses that correspond to short-lived BGP routes, typically for hijacked prefixes. These trends suggest that developing algorithms to identify botnet membership, filtering email messages based on network-leve l properties (which are less variable than email content), and improving the security of the Internet routing infrastructure, may prove to be extremely effective for combating spam.
Design, Synthesis, and Structure–Activity Relationship Studies of Fluorescent Inhibitors of Cycloxygenase-2 as Targeted Optical Imaging Agents (2013)

Cycloxygenase-2 (COX-2) is an attractive target for molecular imaging because it is an inducible enzyme that is expressed in response to inflammatory and proliferative stimuli. Recently, we reported that conjugation of indomethacin with carboxy-X-rhodamine dyes results in the formation of effective, targeted, optical imaging agents able to detect COX-2 in inflammatory tissues and premalignant and malignant tumors (Uddin et al. Cancer Res. 2010, 70, 3618-3627). The present paper summarizes the details of the structure-activity relationship (SAR) studies performed for lead optimization of these dyes. A wide range of fluorescent conjugates were designed and synthesized, and each of them was tested for the ability to selectively inhibit COX-2 as the purified protein and in human cancer cells. The SAR study revealed that indomethacin conjugates are the best COX-2-targeted agents compared to the other carboxylic acid-containing nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2-selective inhibitors (COXIBs). An n-butyldiamide linker is optimal for tethering bulky fluorescent functionalities onto the NSAID or COXIB cores. The activity of conjugates also depends on the size, shape, and electronic properties of the organic fluorophores. These reagents are taken up by COX-2-expressing cells in culture, and the uptake is blocked by pretreatment with a COX inhibitor. In in vivo settings, these reagents become highly enriched in COX-2-expressing tumors compared to surrounding normal tissue, and they accumulate selectively in COX-2-expressing tumors as compared with COX-2-negative tumors grown in mice. Thus, COX-2-targeted fluorescent inhibitors are useful for preclinical and clinical detection of lesions containing elevated levels of COX-2.
Economic Value of Pregnancy in Dairy Cattle (2006)

The objective of this study was to estimate the value of pregnancy for dairy cows. Effects of the stage of gestation, stage of lactation, lactation number, milk yield, milk price, replacement heifer cost, probability of pregnancy, probability of involuntary culling, and breeding decisions were studied. A bioeconomic model was used, and breeding and replacement decisions were optimized. A general Holstein herd in the United States was modeled. The average value of a new pregnancy was $278. The value of a new pregnancy increased with days in milk early in lactation but typically decreased later in lactation. Relatively high-producing cows and first-lactation cows reached greater values, and their values peaked later in lactation. The average cost of a pregnancy loss (abortion) was $555. The cost of a pregnancy loss typically increased with gestation length. Sensitivity analyses showed that an increased probability of pregnancy, an increased persistency of milk yield, and a smaller replacement heifer cost greatly reduced the average value of a pregnancy. The value of a new pregnancy was negative for relatively high-producing first-lactation cows when persistency of lactation and the probability of pregnancy were increased. Breeding was delayed when the value of pregnancy was negative. Changes in milk price, absolute milk yield, and probability of involuntary culling had less effect on the value of pregnancy. The value of pregnancy and optimal breeding decisions for individual cows were greatly dependent on the predicted daily milk yield for the remaining period of lactation. An improved understanding of the value of pregnancy may support decision making in reproductive management when resources are limited.