gebhart/patrepeval huggingface dataset:
A Divergence in the MAP Kinase Regulatory Network Defined by MEK Kinase and Raf (1993)

Mitogen-activated protein kinases (MAPKs) are rapidly phosphorylated and activated in response to various extracellular stimuli in many different cell types. Such regulation of MAPK results from sequential activation of a series of protein kinases. The kinases that phosphorylate MAPKs, the MAP kinase kinases (MEKs) are also activated by phosphorylation. MEKs are related in sequence to the yeast protein kinases Byr1 (from Schizosaccharomyces pombe) and Ste7 (from Saccharomyces cerevisiae), which function in the pheromone-induced signaling pathway that results in mating. Byr1 and Ste7 are in turn regulated by the protein kinases Byr2 and Ste11. The amino acid sequence of the mouse homolog of Byr2 and Ste11, denoted MEKK (MEK kinase), was elucidated from a complementary DNA sequence encoding a protein of 672 amino acid residues (73 kilodaltons). MEKK was expressed in all mouse tissues tested, and it phosphorylated and activated MEK. Phosphorylation and activation of MEK by MEKK was independent of Raf, a growth factor-regulated protein kinase that also phosphorylates MEK. Thus, MEKK and Raf converge at MEK in the protein kinase network mediating the activation of MAPKs by hormones, growth factors, and neurotransmitters.
Radiolysis of Cystine in Aqueous Solution by Gamma Irradiation (1966)

From several experiments on oxidative radiolysis of cystine in aircontaining aqueous solution a scheme of radiolytic mechanism was proposed as follows: Chromatographic behaviors of these intermediate products and the radiolytic process were described
Differential Bacterial Surface Display of Peptides by the Transmembrane Domain of OmpA (2009)

Peptide libraries or antigenic determinants can be displayed on the surface of bacteria through insertion in a suitable outer membrane scaffold protein. Here, we inserted the well-known antibody epitopes 3xFLAG and 2xmyc in exterior loops of the transmembrane (TM) domain of OmpA. Although these highly charged epitopes were successfully displayed on the cell surface, their levels were 10-fold reduced due to degradation. We verified that the degradation was not caused by the absence of the C-terminal domain of OmpA. In contrast, a peptide that was only moderately charged (SA-1) appeared to be stably incorporated in the outer membrane at normal protein levels. Together, these results suggest that the display efficiency is sensitive to the charge of the inserted epitopes. In addition, the high-level expression of OmpA variants with surface-displayed epitopes adversely affected growth in a strain dependent, transient manner. In a MC4100 derived strain growth was affected, whereas in MC1061 derived strains growth was unaffected. Finally, results obtained using a gel-shift assay to monitor beta-barrel folding in vivo show that the insertion of small epitopes can change the heat modifiability of the OmpA TM domain from 'aberrant' to normal, and predict that some beta-barrels will not display any significant heat-modifiability at all.
Anti-tumor efficacy and biomarker evaluation of agonistic anti-OX40 antibodies in preclinical models (2014)

Meeting abstracts OX40, a TNFRSF member, is a co-stimulatory molecule expressed on antigen experienced effector T (Teff) and regulatory T (Treg) cells, including infiltrating cells in mouse and human tumors. Activation of OX40 by agonistic antibodies is hypothesized to promote anti-tumor immunity
A robust, optimization-based approach for approximate answering of aggregate queries (2001)

The ability to approximately answer aggregation queries accurately and efficiently is of great benefit for decision support and data mining tools. In contrast to previous sampling-based studies, we treat the problem as an optimization problem whose goal is to minimize the error in answering queries in the given workload. A key novelty of our approach is that we can tailor the choice of samples to be robust even for workloads that are “similar” but not necessarily identical to the given workload. Finally, our techniques recognize the importance of taking into account the variance in the data distribution in a principled manner. We show how our solution can be implemented on a database system, and present results of extensive experiments on Microsoft SQL Server 2000 that demonstrate the superior quality of our method compared to previous work.
Recombinant chicken interferon: a potent antiviral agent that lacks intrinsic macrophage activating factor activity (1995)

Crude preparations of chicken interferon (ChIFN) from various sources contain both antiviral and macrophage-activating factor (MAF) activity. Previous serological data indicated that unlike mammals, birds might express only a single type of IFN in response to viruses and mitogens that exhibits both activities. We have now expressed a complementary DNA for virus-induced ChIFN in transfected COS cells and in Escherichia coli. Purified recombinant ChIFN is a powerful antiviral agent and has high Mx promoter-inducing activity. However, as the sole agent, recombinant ChIFN lacks MAF activity: it does not induce the secretion of nitric oxide in primary monocyte-derived chicken macrophages. A neutralizing antiserum prepared against cloned ChIFN blocks most of the antiviral and Mx promoter-inducing activity present in preparations of natural ChIFN, but does not inhibit the MAF activity. These results demonstrate that chicken cells can be induced to secrete a novel cytokine which probably represents the avian homolog of mammalian IFN-gamma.
Radiofrequency catheter ablation of ventricular tachycardia in patients with coronary artery disease. (1993)

The results of this study demonstrate that RF ablation of hemodynamically stable VT is feasible as adjunctive therapy in selected patients with coronary artery disease.
The two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior. (1993)

The metastatic pancreas carcinoma cell line BSp73ASML produces a variety of different splice variants of the transmembrane glycoprotein CD44. The NH2-terminal portions are identical and heavily glycosylated. The variant sequences are inserted just outside the transmembrane region of the molecules. The two most abundant variants have 162 and 85 extra amino acids, respectively. When individually expressed, these suffice to establish metastatic properties in the nonmetastatic tumor cell line BSp73AS, as assayed by the spontaneous metastasis protocol.
Eliminating a Region of Respiratory Syncytial Virus Attachment Protein Allows Induction of Protective Immunity without Vaccine-enhanced Lung Eosinophilia (1998)

In a murine model of respiratory syncytial virus disease, prior sensitization to the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced illness. Three different approaches were taken to dissect the region of G responsible for enhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mice sensitized by scarification with recombinant vaccinia virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge with wild-type respiratory syncytial virus (RSV). These studies identified residues 193-205 to be responsible for G-induced weight loss and lung eosinophilia and showed that this region was not was not necessary for induction of protective immunity. Third, mice were sensitized using an rVV that expressed only amino acids 124-203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weight loss and eosinophilia. This is the first time that a region within RSV (amino acids 193-203) has been shown to be responsible for induction of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G protein without inducing a pathological response.
Simulation of AZ-PN100 Resist Pattern Fluctuation in X-Ray Lithography, Including Synchrotron Beam Polarization (1993)

A new simulation model for nanometer-scale pattern fluctuation in X-ray lithography is presented and applied to a study of AZ-PN100 negative chemical amplification resist. The exposure simulation considers polarized photons from a synchrotron radiation (SR) source. Monte Carlo simulation of Auger and photoelectron generation is followed by electron scattering simulation to determine the deposited energy distribution at the nanometer scale, including beam polarization effects. An acid-catalyst random walk model simulates the post-exposure bake (PEB) step. Fourier transform infrared (FTIR) spectroscopy and developed resist thickness measurements are used to fit PEB and rate models for AZ-PN100. A polymer removal model for development simulation predicts the macroscopic resist shape and pattern roughness. The simulated 3σ linewidth variation is in excess of 24 nm. Simulation also shows a detrimental effect if the beam polarization is perpendicular to the line. Simulation assuming a theoretical ideal exposure yields a 50 nm minimum line for standard process conditions.
Can Personality Be Changed? The Role of Beliefs in Personality and Change (2008)

Using recent research, I argue that beliefs lie at the heart of personality and adaptive functioning and that they give us unique insight into how personality and functioning can be changed. I focus on two classes of beliefs—beliefs about the malleability of self-attributes and expectations of social acceptance versus rejection—and show how modest interventions have brought about important real-world changes. I conclude by suggesting that beliefs are central to the way in which people package their experiences and carry them forward, and that beliefs should play a more central role in the study of personality.
Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? (1990)

Infants born to hepatitis B virus carrier mothers, who express a secreted form of the nucleocapsid antigen designated HBeAg, invariably become persistently infected. To investigate the role of immunologic tolerance mechanisms in chronic infection of the newborn, we have generated HBeAg-expressing transgenic mice. HBeAg-expressing transgenic mice were tolerant to both HBeAg and the nonsecreted nucleocapsid (hepatitis B cor antigen/HBcAg) at the T-cell level. Transgenic mice did not produce antibody to HBeAg but did produce anti-HBc antibody in vivo and in vitro. The coexistence of tolerance to HBc/HBe T-cell determinants and anti-HBc antibody production in vivo parallels the immunologic status of neonates born to carrier mothers. It was also demonstrated that the maintenance of T-cell tolerance to HBcAg/HBeAg required the continued presence of the tolerogen and in its absence persisted for less than 16 weeks. The reversibility of T-cell tolerance to HBcAg/HBeAg may explain the inverse correlation between age of infection and rates of viral persistence. These observations suggest that a function of the HBeAg may be to induce immunologic tolerance in utero. Expression of HBeAg may represent a viral strategy to guarantee persistence after perinatal infection.
Phenotypic and genetic diversity of rice seed-associated bacteria and their role in pathogenicity and biological control (2009)

This line of work contributes to a better understanding of the microbial diversity present on rice seed and stresses its importance as a carrier of antagonists and pathogens.
Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm. (1990)

A major source of oxidative stress in animals is plant stress metabolites, also termed phytoalexins. The aromatic hydrocarbon-responsive [Ah] gene battery is considered here as a model system in which we can study metabolically coordinated enzymes that respond to phytoalexin-induced oxidative stress. In the mouse, the [Ah] battery comprises at least six genes: two Phase I genes, CYP1A1 and CYP1A2; and four Phase II genes, Nmo-1, Aldh-1, Ugt-1, and Gt-1. All six genes appear to be regulated positively by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other ligands of the Ah receptor. In the absence of foreign inducer, the control of Nmo-1 gene expression is independent of the control of CYP1A1 and CYP1A2 gene expression. The radiation deletion homozygote c14CoS/c14CoS mouse is lacking about 1.1 centiMorgans of chromosome 7. Although having no detectable CYP1A1 or CYP1A2 activation, the untreated c14CoS/c14CoS mouse exhibits markedly elevated transcripts of the Nmo-1 gene and three growth arrest- and DNA damage-inducible (gadd) genes. These data suggest that the missing region on chromosome 7 in the c14CoS/c14CoS mouse contains a gene(s), which we propose to call Nmo-1n, encoding a trans-acting factor(s) that is a negative effector of the Nmo-1 and gadd genes. The three other [Ah] battery Phase II genes behave similarly to Nmo-1 in the c14CoS/c14CoS mouse. This coordinated response to oxidative stress and DNA damage, by way of the release of a mammalian battery of genes from negative control, bears an interesting resemblance to the SOS response in bacteria.
Antileukemic activity of recombinant humanized M195-gelonin immunotoxin in nude mice. (1996)

A leukemia-selective immunotoxin was constructed by linking recombinant gelonin (rGel), a single chain ribosome inhibitory protein, to recombinant humanized M195 antibody (HuM195), which recognizes the cell-surface protein designated CD33. CD33 is an antigen found on myeloid leukemia blasts as well as myeloid progenitor cells but it is not expressed in detectable amounts on the ultimate hematopoietic progenitor stem cell. Our previous studies indicated that a non-recombinant humanized immunotoxin displayed specific, potent toxicity towards CD33-positive cells but not to CD33-negative cells in vitro. In the current study, a recombinant humanized immunotoxin, HuM195-rGel, was evaluated in vivo in a nude mouse model of human myeloid leukemias. HuM195-rGel was found to target leukemia cells rapidly in vivo and was subsequently internalized into the cells. For trials in vivo, nude mice were injected (ip) with 10(7) log-phase HL60 human leukemia cells 10 days prior to the start of i.p. HuM195-rGel treatments. HuM195-rGel demonstrated significant tumor suppressive activity in this model. While all mice treated with either saline, rGel alone, or HuM195 plus unconjugated rGel (at 10 or 14 days after transplantation) had rapid tumor growth or early deaths, 50% of mice treated with HuM195-rGel failed to develop leukemic tumors for 5 months and the 50% had significantly retarded tumor growth after treatment with HuM195-rGel. Mice treated at later times (28 days after transplantation of leukemia cells) also showed delayed leukemia cell growth, but no cures. These data show that HuM195-rGel can target leukemia cells in vivo and can result in pronounced anti-leukemic effects.
Generation of anti-Notch antibodies and their application in blocking Notch signalling in neural stem cells (2012)

Notch signalling occurs via direct cell-cell interactions and plays an important role in linking the fates of neighbouring cells. There are four different mammalian Notch receptors that can be activated by five cell surface ligands. The ability to inhibit specific Notch receptors would help identify the roles of individual family members and potentially provide a means to study and control cell differentiation. Anti-Notch antibodies in the form of single chain Fvs were generated from an antibody phage display library by selection on either the ligand binding domain or the negative regulatory region (NRR) of Notch1 and Notch2. Six antibodies targeting the NRR of Notch1 and four antibodies recognising the NRR of Notch2 were found to prevent receptor activation in cell-based luciferase reporter assays. These antibodies were potent, highly specific inhibitors of individual Notch receptors and interfered with endogenous signalling in stem cell systems of both human and mouse origin. Antibody-mediated inhibition of Notch efficiently down-regulated transcription of the immediate Notch target gene hairy and enhancer of split 5 (Hes5) in both mouse and human neural stem cells and revealed a redundant regulation of Hes5 in these cells as complete down-regulation was seen only after simultaneous blocking of Notch1 and Notch2. In addition, these antibodies promoted differentiation of neural stem cells towards a neuronal fate. In contrast to the widely used small molecule γ-secretase inhibitors, which block all 4 Notch receptors (and a multitude of other signalling pathways), antibodies allow blockade of individual Notch family members in a highly specific way. Specific inhibition will allow examination of the effect of individual Notch receptors in complex differentiation schemes regulated by the co-ordinated action of multiple signalling pathways.
The chemokine receptor CXCR4 is required for outgrowth of colon carcinoma micrometastases. (2003)

CXCR4, the receptor for the chemokine stromal cell-derived factor (SDF)-1 (CXCL12), is involved in lymphocyte trafficking. We have demonstrated previously that it is required for invasion of lymphoma cells into tissues and therefore essential for lymphoma metastasis. CXCR4 is also expressed by carcinoma cells, and CXCR4 antibodies were recently shown to reduce metastasis of a mammary carcinoma cell line. This was also ascribed to impaired invasion. We have blocked CXCR4 function in CT-26 colon carcinoma cells by transfection of SDF-1, extended with a KDEL sequence. The SDF-KDEL protein is retained in the endoplasmic reticulum by the KDEL-receptor and binds CXCR4, which is thus prevented from reaching the cell surface. We found that metastasis of these cells to liver and lungs was greatly reduced and often completely blocked. Surprisingly, however, our observations indicate that this was not attributable to inhibition of invasion but rather to impairment of outgrowth of micrometastases: (a) in contrast to the lymphoma cells, metastasis was not affected by the transfected S1 subunit of pertussis toxin. S1 completely inhibited Gi protein signaling, which is required for SDF-1-induced invasion; (b) CXCR4 levels were very low in CT-26 cells grown in vitro but strongly up-regulated in vivo. Strong up-regulation was not seen in the lungs until 7 days after tail vein injection. CXCR4 can thus have no role in initial invasion in the lungs; and (c) CXCR4-deficient cells did colonize the lungs to the same extent as control cells and survived. However, they did not expand, whereas control cells proliferated rapidly after a lag period of > or = 7 days. We conclude that CXCR4 is up-regulated by the microenvironment and that isolated metastatic cells are likely to require CXCR4 signals to initiate proliferation. Our results suggest that CXCR4 inhibitors have potential as anticancer agents to suppress outgrowth of micrometastases.
Less After-the-Fact: Investigative visual analysis of events from streaming twitter (2013)

News and events are traditionally broadcasted in an “After-the-Fact” manner, where the masses react to news formulated by a group of professionals. However, the deluge of information and real-time online social media sites have significantly changed this information input-output cycle, allowing the masses to report real-time events around the world. Specifically, the use of Twitter has resulted in the creation of a digital wealth of knowledge that directly associates to such events. Although governments and industries acknowledge the value of extracting events from the TwitterSphere, unfortunately the sheer velocity and volume of tweets poses significant challenges to the desired event analysis. In this paper, we present our Geo and Temporal Association Creator (GTAC) which extracts structured representations of events from the Twitter stream. GTAC further supports event-level investigative analysis of social media data through interactively visualizing the event indicators (who, when, where, and what). Using GTAC, we are trying to create a near real-time analysis environment for analysts to identify event structures, geographical distributions, and key indicators of emerging events.
Short‐term Effects of Sacral Nerve Stimulation for IdiopathicSlow Transit Constipation (2002)

This study assessed the short-term clinical and physiological effect of continuous sacral nerve stimulation in patients with slow transit constipation. Some patients with idiopathic slow transit constipation are unresponsive to conservative treatments, while colectomy has a variable and poorly predictable outcome. Sacral nerve stimulation is a less invasive and reversible procedure that enables direct neuromodulation of the pelvic floor and hindgut. It has been used successfully in the treatment of urologic disorders and fecal incontinence, and some of these patients with concurrent constipation have also noted improved stool frequency and rectal evacuation. Eight women (median age 47 years, median symptom duration 31 years, median stool frequency once per 6 days) were implanted with a temporary percutaneous stimulating S3 electrode for 3 weeks, attached to an external stimulator (Medtronic, Minneapolis,USA). A bowel symptom diary card, anorectal physiological studies, and a radiopaque marker transit study were completed before and during stimulation. Two patients had cessation or marked diminution of symptoms, including normalization of bowel frequency. Colonic transit did not return to normal in any patient. Rectal sensory threshold to distension was decreased during stimulation. Percutaneous temporary sacral nerve stimulation symptomatically improved a minority of patients with resistant idiopathic slow transit constipation. Sensory function was altered by stimulation. Further studies are required to identify patients who may benefit and to assess a range of stimulation parameters.
Peripheral modulation of duodenal and colonic motility and arterial pressure by neuropeptide Y, neuropeptide Y fragment 13–36, peptide YY, and pancreatic polypeptide in rats: cholinergic mechanisms (1993)

The pancreatic polypeptide-fold (PP-fold) peptides neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) (500 pmol/kg) increased duodenal and colonic intraluminal pressure of urethane-anesthesized rats following intravenous (i.v.) bolus injections. Increases in mean arterial pressure (MAP) accompanied the excitatory effects of NPY and PYY on gastrointestinal motility in these rats during the same time period. Atropine attenuated PYY's excitatory effect on duodenal pressure of rats. Excitatory effects of NPY, PYY, and PP (i.v.) on rat colon were not mediated via the muscarinic receptors. In the presence of hexamethonium, a nicotinic antagonist, PP (i.v.) increased colonic pressure to a greater extent than when administered alone. This observation suggested that PP had an inhibitory effect on colonic motility, which was not apparent as a result of the larger excitatory component. The nicotinic antagonist did not modulate the effects of peripherally administered NPY or PYY on duodenal or colonic motility in anesthetized rats. The Y2 receptor ligand, NPY (13-36) (i.v.) (500 pmol/kg), increased duodenal and colonic pressure in rats to the same extent as the full NPY molecule. Therefore, the peripheral effect of PYY and NPY on duodenal and colonic motility in rats may be mediated via Y2 receptors. NPY and PYY (i.v.) initially increased MAP, which then return to baseline values. Unlike NPY and PYY (i.v.) which produced short-term hypertensive effects PP (i.v. decreased MAP. Atropine did not attenuate the hypertensive effects of PYY and NPY (i.v.); however, the hypotensive effect of PP (i.v.) was blocked by atropine. The effects of the PP-fold peptides on MAP were not altered in the presence of hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)