gebhart/patrepeval huggingface dataset:
Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1. (1998)

Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin. At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice. These elevated levels of serum cholesterol and TG were due mainly to an accumulation of VLDL particles in the circulation. In addition to hyperlipidemia, APOC1 transgenic mice developed dry and scaly skin with loss of hair, dependent on the amount of APOC1 expression in the skin. Since these skin abnormalities appeared in two independent founder lines, a mutation related to the specific insertion site of the human APOC1 gene as the cause for the phenotype can be excluded. Histopathological analysis of high expressor APOC1 transgenic mice revealed a disorder of the skin consisting of epidermal hyperplasia and hyperkeratosis, and atrophic sebaceous glands lacking sebum. In line with these results, epidermal lipid analysis showed that the relative amounts of the sebum components TG and wax diesters in the epidermis of high expressor APOC1 transgenic mice were reduced by 60 and 45%, respectively. In addition to atrophic sebaceous glands, the meibomian glands were also found to be severely atrophic in APOC1 transgenic mice. High expressor APOC1 transgenic mice also exhibited diminished abdominal adipose tissue stores (a 60% decrease compared with wild-type mice) and a complete deficiency of subcutaneous fat. These results indicate that, in addition to the previously reported inhibitory role of apoC1 on hepatic remnant uptake, overexpression of apoC1 affects lipid synthesis in the sebaceous gland and/or epidermis as well as adipose tissue formation. These APOC1 transgenic mice may serve as an interesting in vivo model for the investigation of lipid homeostasis in the skin.
Migration of processes, files, and virtual devices in the MDX operating system (1995)

Load management in distributed systems is usually focused on balancing process execution and communication load. Stress on storage media and I/O-devices is considered only indirectly or disregarded. For I/O-intensive processes this imposes severe restrictions on balancing algorithms: processes have to be placed relative to fixed allocated resources. Therefore, beyond process migration, there is a need for a migration of all operating system objects, like files, pipes, timers, virtual terminals, and print jobs. In addition to new options for balancing cpu loads, this also makes it possible to balance the loads associated with these objects like storage capacity or I/O-bandwidth.This paper presents a concept for a general migration of nearly all operating system objects of a UNIX environment. The migrations of these objects work all in the same UNIX compliant and transparent manner. Objects can be moved throughout a distributed system independently of each other and at any time, according to a user defined policy. The migration mechanism is implemented as part of the MDX operating system; we present performance measurements. We believe that most of the mechanism can also apply to other message-passing based distributed operating systems.
High-Performance Liquid Chromatographic Method Applied to Paralytic Shellfish Poisoning Research (1990)

The use of high performance liquid chromatography (HPLC) for the study of paralytic shellfish poisoning (PSP) has facilitated a greater understanding of the biochemistry and chemistry of the toxins involved. HPLC enables the determination of the type and quantity of the PSP toxins present in biological samples. An overview of the HPLC method is presented that outlines the conditions for both separation and detection of the PSP toxins. Examples of the use of the HPLC method in toxin research are reviewed, including its use in the determination of the enzymatic conversion of the toxins and studies on the movement of the toxins up the marine food chain.
Effect of Solution Silicate on the Precipitation of Barium Sulfate (2012)

The presence of silicate during barium sulfate crystallization has different impacts depending on the pH of the solution. At pH 7 the dominance of the protonated form (H4SiO4) and possible polymerization of the silicate impacts mainly on the aggregation state and on twinning of the barium sulfate formed. At higher pH values (∼10), the silicate ion present is able to influence both morphology and partially substitute for sulfate in the lattice. Interesting fibrous particles are formed under these conditions, but this is not due to mesocrystal formation as the particles are observed to be single crystalline in nature. These fibrous sections are found to be dominant on the surface and are highly porous. These particles are different, however, to the biomorphs formed when crystallization of barium carbonate occurs in the presence of silicate. This is because the speciation of sulfate does not change over a large pH range. The impact of silicate on barium sulfate particles is similar to the impact on calcium carbonate and strontium sulfate crystallization.
amphivasal vascular bundle 1, a Gain-of-Function Mutation of the IFL1/REV Gene, Is Associated with Alterations in the Polarity of Leaves, Stems and Carpels (2004)

In Arabidopsis stems, the vascular bundles in the stele are arranged in a ring-like pattern and the vascular tissues in each bundle are organized in a collateral pattern. We have shown previously that the semidominant amphivasal vascular bundle 1 (avb1) mutation transforms the collateral vascular bundles into amphivasal bundles and disrupts the ring-like arrangement of vascular bundles in the stele. In this study, we show that the avb1 mutation occurred in the putative microRNA 165 target sequence in the IFL1/REV gene and caused an amino acid substitution in the putative sterol/lipid-binding START domain. We present direct evidence that the wild-type IFL1/REV mRNA was cleaved within the microRNA 165 target sequence and the avb1 mutation resulted in an inhibition of cleavage and a higher level accumulation of full-length mRNA, suggesting a role of microRNA 165 in the regulation of IFL1/REV gene expression. In addition to an alteration in vascular patterning, the avb1 mutation also caused dramatic changes in fiber cell wall thickening and organ polarity, including aberrant formation and proliferation of cauline leaves and branches, production of trumpet-shaped leaves with reversed adaxial-abaxial identity, ectopic growth of carpel-like structures on the outer surface of carpels, and fasciation of inflorescence. Ectopic overexpression of the avb1 mutant cDNA not only phenocopied most of the avb1 mutant phenotypes but also led to additional novel phenotypes such as formation of leaves with extremely narrow blades and ectopic production of branches in the axil of siliques. Taken together, these results suggest that the avb1 gain-of-function mutation of the IFL1/REV gene alters the positional information that determines vascular patterning and organ polarity.
Electroporation for DNA immunization: clinical application (2010)

DNA immunization is an attractive technology owing to its potential to induce balanced and long-lived immune responses. However, progress into the clinic has been hampered by the relatively low magnitude of the immune response typically induced following administration in large target species, which is likely due to low transfection efficiency as well as insufficient recruitment of antigen-presenting cells to the injection site. Electroporation addresses both of these limitations by inducing transiently enhanced cell membrane permeability, thus facilitating uptake of the DNA into the host cell and creating a low level of inflammation conducive to enhanced influx of antigen-presenting cells to the injection site. Consequently, electroporation-mediated delivery of DNA vaccines results in very significant improvements in the transfection efficiency and immune responses in comparison to conventional injection. Importantly, electroporation is effective in virtually every animal model tested to date and has a favorable safety profile, which is promising for clinical application. In support of the potential for electroporation in human disease situations, early clinical results suggest that the immunogenicity of DNA vaccines is greatly improved when delivered with electroporation.
An effective human iris code with low complexity (2005)

A human iris coding technique is reported based upon differences in the power spectrum of fragments from normalized iris images. The procedure has been applied to a set of 2174 images from 308 eyes and tuned over a range of parameters. For identity recognition, 100% correct recognition is achieved using a weighted Hamming distance metric. For identity verification, a variable threshold is applied to the distance metric and the false acceptance and false rejection rates are recorded. After tuning the various parameters, the method achieves the lowest false acceptance rate at the point of first false rejection amongst the three algorithms tested, as well as the lowest complexity.
Targeting autophagy augments the anticancer activity of the histone deacetylase inhibitor SAHA to overcome Bcr-Abl–mediated drug resistance (2007)

Novel therapeutic strategies are needed to address the emerging problem of imatinib resistance. The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) is being evaluated for imatinib-resistant chronic myelogenous leukemia (CML) and has multiple cellular effects, including the induction of autophagy and apoptosis. Considering that autophagy may promote cancer cell survival, we hypothesized that disrupting autophagy would augment the anticancer activity of SAHA. Here we report that drugs that disrupt the autophagy pathway dramatically augment the antineoplastic effects of SAHA in CML cell lines and primary CML cells expressing wild-type and imatinib-resistant mutant forms of Bcr-Abl, including T315I. This regimen has selectivity for malignant cells and its efficacy was not diminished by impairing p53 function, another contributing factor in imatinib resistance. Disrupting autophagy by chloroquine treatment enhances SAHA-induced superoxide generation, triggers relocalization and marked increases in the lysosomal protease cathepsin D, and reduces the expression of the cathepsin-D substrate thioredoxin. Finally, knockdown of cathepsin D diminishes the potency of this combination, demonstrating its role as a mediator of this therapeutic response. Our data suggest that, when combined with HDAC inhibitors, agents that disrupt autophagy are a promising new strategy to treat imatinib-refractory patients who fail conventional therapy.
Asthma on Tristan da Cunha: Looking for the Genetic Link. The University of Toronto Genetics of Asthma Research Group (1996)

Although asthma has a significant heritable component, the mode of inheritance remains controversial because of the complexity of the disease and the influence of environmental factors. Isolated, inbred populations serve to reduce variability, thus increasing the probability of gene localization. We studied the inbred population of the remote island of Tristan da Cunha to document asthma prevalence for the purpose of genetic linkage analysis. Medical histories and skin atopy were determined on 282 islanders, representing 97% of the population, and airway responsiveness was measured in 254; 226 by methacholine challenge (tidal breathing method) and 28 by bronchodilator response (400 micrograms salbutamol aerosol). Blood samples were collected from 275 islanders. Participants ranged in age from 3 to 94 yr. Asthma was defined as increased airway responsiveness (AR+: PC20 < 4 mg/ml or > or = 15% increase in FEV1 postbronchodilator) combined with a positive history (Hx+). Fifty-seven percent of the islanders had at least partial evidence of asthma (Hx+ and/or AR+) and 23% had a definitive diagnosis of asthma (AR+ with Hx+). Overall 47% of the population were atopic, atopy was proportionally higher in asthmatics (74%) than nonasthmatics (32%; p < 0.01). Analysis of the methacholine dose-response curves demonstrated that asthmatics were significantly (p < 0.01) more responsive than those with AR+ only, and nonasthmatics (AR-, Hx-) were more responsive than laboratory control subjects (p < 0.05), suggesting that these islanders may also carry an airway hyperresponsiveness gene. A frequency plot of the percent fall in FEV1 for all Hx- subjects compared with control data suggests a bimodal distribution consistent with a major gene mechanism for airway responsiveness. Genealogy mapping revealed that the islanders are direct descendants of the 15 original settlers, and historical records suggest at least two founders may have been asthmatic. The data confirm previous reports of a high asthma prevalence on Tristan and support the postulate that this prevalence is a result of gene enrichment occurring in isolated populations by virtue of extensive inbreeding and a probable founder effect.
Non-Autoregressive Neural Machine Translation (2017)

Existing approaches to neural machine translation condition each output word on previously generated outputs. We introduce a model that avoids this autoregressive property and produces its outputs in parallel, allowing an order of magnitude lower latency during inference. Through knowledge distillation, the use of input token fertilities as a latent variable, and policy gradient fine-tuning, we achieve this at a cost of as little as 2.0 BLEU points relative to the autoregressive Transformer network used as a teacher. We demonstrate substantial cumulative improvements associated with each of the three aspects of our training strategy, and validate our approach on IWSLT 2016 English-German and two WMT language pairs. By sampling fertilities in parallel at inference time, our non-autoregressive model achieves near-state-of-the-art performance of 29.8 BLEU on WMT 2016 English-Romanian.
Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor (1997)

Previous studies suggest that the core protein of hepatitis C virus (HCV) has a pleiotropic function in the replication cycle of the virus. To understand the role of this protein in HCV pathogenesis, we used a yeast two-hybrid protein interaction cloning system to search for cellular proteins physically interacting with the HCV core protein. One such cellular gene was isolated and characterized as the gene encoding the lymphotoxin-beta receptor (LT-betaR). In vitro binding analysis demonstrated that the HCV core protein binds to the C-terminal 98 amino acids within the intracellular domain of the LT-betaR that is involved in signal transduction, although the binding affinity of the full-length HCV core protein was weaker than that of its C-terminally truncated form. Our results also indicated that the N-terminal 40-amino-acid segment of the HCV core protein was sufficient for interaction with LT-betaR and that the core protein could form complexes with the oligomeric form of the intracellular domain of LT-betaR, which is a prerequisite for downstream signaling of this receptor. Similar to other members of the tumor necrosis factor (TNF) receptor superfamily, LT-betaR is involved in the cytotoxic effect of the signaling pathway, and thus we have elucidated the biological consequence of interaction between the HCV core protein and LT-betaR. Our results indicated that in the presence of the synergizing agent gamma interferon, the HCV core protein enhances the cytotoxic effects of recombinant forms of LT-betaR ligand in HeLa cells but not in hepatoma cells. Furthermore, this enhancement of the cytolytic activity was cytokine specific, since in the presence of cycloheximide, the expression of the HCV core protein did not elicit an increase in the cytolytic activity of TNF in both HeLa and hepatoma cells. In summary, the HCV core protein can associate with LT-betaR, and this protein-protein interaction has a modulatory effect on the signaling pathway of LT-betaR in certain cell types. Given the known roles of LT-betaR/LT-alpha1,beta2 receptor-ligand interactions in the normal development of peripheral lymphoid organs and in triggering cytolytic activity and NF-kappaB activation in certain cell types, our finding implies that the HCV core protein may aggravate these biological functions of LT-betaR, resulting in pathogenesis in HCV-infected cells.
Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides. (1996)

gp1OO is a melanocytic lineage-specific antigen recognized by tumor-infiltrating lymphocytes, the adoptive transfer of which is associated with tumor regression in melanoma patients. In this study, peripheral blood mononuclear cells (PBMCs) were harvested from HLA-A2+ melanoma patients before and after immunization with G9-209 (ITDQVPFSY), G9-280 (YLEPGPVTA), or G9-154 (KTWGQYWQV) peptides in Incomplete Freund's Adjuvant and were tested for the ability to be sensitized in vitro using PBMCs pulsed with the native peptides. In addition, PBMCs from patients receiving the G9-209 or G9-280 peptide were stimulated in vitro with peptides modified at anchor residues to enhance binding to HLA-A2: G9-209/2M (IMDQVPFSY) or G9-280-9V (YLEPGPVTV). In patients immunized with G9-209, a single in vitro restimulation with G9-209/2M resulted in the generation of specific antipeptide lymphocytes from seven of seven postimmune PBMCs and only three of seven preimmune PBMCs. In patients immunized with G9-280, a single in vitro restimulation with G9-280/9V resulted in the generation of specific antipeptide lymphocytes from five of six postimmune PBMCs and four of six preimmune PBMCs. In almost all cases, CTLs raised against modified epitopes were capable of recognizing targets displaying the native nonamers. Several anti-G9-209 and anti-G9-209/2M CTLs also demonstrated specific lysis of, and specific IFN-gamma release in response to, gp1OO+-established cell lines. Thus, using peptides modified to enhance immunogenicity for in vitro stimulation improved the sensitivity of immune monitoring of patients immunized with synthetic peptides. These results demonstrate that immunization with a peptide derived from a tumor-associated protein such as gp100 can provoke a measurable antitumor immune response in cancer patients.
Improving static and dynamic registration in an optical see-through HMD (1994)

In Augmented Reality, see-through HMDs superimpose virtual 3D objects on the real world. This technology has the potential to enhance a user's perception and interaction with the real world. However, many Augmented Reality applications will not be accepted until we can accurately register virtual objects with their real counterparts. In previous systems, such registration was achieved only from a limited range of viewpoints, when the user kept his head still. This paper offers improved registration in two areas. First, our system demonstrates accurate static registration across a wide variety of viewing angles and positions. An optoelectronic tracker provides the required range and accuracy. Three calibration steps determine the viewing parameters. Second, dynamic errors that occur when the user moves his head are reduced by predicting future head locations. Inertial sensors mounted on the HMD aid head-motion prediction. Accurate determination of prediction distances requires low-overhead operating systems and eliminating unpredictable sources of latency. On average, prediction with inertial sensors produces errors 2-3 times lower than prediction without inertial sensors and 5-10 times lower than using no prediction at all. Future steps that may further improve registration are outlined.
Effects of Nonsteroidal Antiestrogens in the in vitro Rat Uterus (1992)

We have studied the effect of nonsteroidal antiestrogens on rat uterine contractions induced by oxytocin (8 nmol/l), methacholine (10 mumol/l), prostaglandin F2 alpha (1 mumol/l), KCl (60 mmol/l) and CaCl2 (6 mmol/l). In a concentration-dependent way, the antiestrogens tamoxifen, clomiphene, nafoxidine and ethamoxytriphetol inhibited the amplitude and frequency of the oxytocin-induced contractions and the contraction produced by CaCl2. At a concentration of 30 mumol/l the four drugs inhibited the contractions induced by methacholine and prostaglandin F2 alpha. They also relaxed the tonic contraction to KCl in a concentration-dependent way. This action was partially counteracted by CaCl2 (0.1-10 mmol/l). Bay k 8644 (0.3 nmol/l to 3 mumol/l) only partially reversed the inhibition by ethamoxytriphetol (0.1 mmol/l) of CaCl2 (6 mmol/l)-induced contractions. The steroidal antiestrogen, ICI 164,384, which lacks agonist activity, had an inhibitory effect (44 +/- 4%, n = 7) on KCl-induced contractions only at a concentration of 0.1 mmol/l. However, the quaternary analogue of tamoxifen (tamoxifen ethyl bromide) produced 86 +/- 3% relaxation of the KCl-induced contracture (IC50 1.52 +/- 0.1 mumol/l, n = 10) and this effect was counteracted by addition of CaCl2. Taken together the results indicate that the inhibitory effects of nonsteroidal antiestrogens on rat uterine contractions could be mediated by an action to block Ca2+ entry through an agonist action on extracellular estrogen receptors.
Inhibitors of poly ADP-ribose polymerase (PARP) induce apoptosis of myeloid leukemic cells: potential for therapy of myeloid leukemia and myelodysplastic syndromes (2009)

PARP inhibitors, KU-0058948 and PJ34, induced cell cycle arrest and apoptosis of primary myeloid leukemic cells and myeloid leukemic cell lines in vitro. Immunofluorescence analysis also revealed that PARP inhibitor sensitivity in these leukemic cells was due to a defect in homologous recombination DNA repair. Addition of 5' aza-2'-deoxycytidine failed to increase the cytotoxicity of PARP inhibitors. In contrast, MS275 potentiated the cytotoxic effect of KU-0058948 and PJ34 in all PARP inhibitor-sensitive leukemic cells. Immunofluorescence analysis supported the idea that histone deacetylase inhibitors potentiate cytotoxicity by inhibiting DNA repair processes. Conclusions On the basis of the data presented here, we suggest that PARP inhibitors can potentially exploit defects in double-strand DNA break repair in leukemic cells, paving the way for testing the therapeutic potential of these agents in myelodysplastic syndromes and acute myeloid leukemia.
Inversing the natural hydrogen bonding rule to selectively amplify GC-rich ADAR-edited RNAs (2008)

DNA complementarity is expressed by way of three hydrogen bonds for a G:C base pair and two for A:T. As a result, careful control of the denaturation temperature of PCR allows selective amplification of AT-rich alleles. Yet for the same reason, the converse is not possible, selective amplification of GC-rich alleles. Inosine (I) hydrogen bonds to cytosine by two hydrogen bonds while diaminopurine (D) forms three hydrogen bonds with thymine. By substituting dATP by dDTP and dGTP by dITP in a PCR reaction, DNA is obtained in which the natural hydrogen bonding rule is inversed. When PCR is performed at limiting denaturation temperatures, it is possible to recover GC-rich viral genomes and inverted Alu elements embedded in cellular mRNAs resulting from editing by dsRNA dependent host cell adenosine deaminases. The editing of Alu elements in cellular mRNAs was strongly enhanced by type I interferon induction indicating a novel link mRNA metabolism and innate immunity.