gebhart/patrepeval huggingface dataset:
In vitro packaging and replication of individual genomic segments of bacteriophage phi 6 RNA (1992)

The genome of bacteriophage phi 6 contains three segments of double-stranded RNA. Procapsid structures whose formation was directed by cDNA copies of the large genomic segment are capable of packaging the three viral message sense RNAs in the presence of ATP. Addition of UTP, CTP, and GTP results in the synthesis of minus strands to form double-stranded RNA. In this report, we show that procapsids are capable of taking up any of the three plus-strand single-stranded RNA segments independently of the others. In manganese-containing buffers, synthesis of the corresponding minus strand takes place. In magnesium-containing buffers, individual message sense viral RNA segments were packaged, but minus-strand replication did not take place unless all three viral single-stranded RNA segments were packaged. Since the conditions of packaging in magnesium buffer more closely resemble those in vivo, these results indicated that there is no specific order or dependence in packaging and that replication is regulated so that it does not begin until all segments are in place.
Physicochemical, Catalytic, and Immunochemical Properties of Fumarases Crystallized Separately from Mitochondrial and Cytosolic Fractions of Rat Liver1 (1981)

Fumarases located in the cytosolic and mitochondrial fractions were separately purified and crystallized from rat liver. Polyacrylamide gel electrophoresis of these two crystallized fumarases in the presence of dodecyl sulfate gave a single protein band in a position corresponding to a molecular weight of about 49, 000 in each case. A single protein band was also obtained by acidic polyacrylamide gel electrophoresis of the cytosolic or mitochondrial fumarase in the presence of 8 M urea. In both experiments, the subunits of these two fumarases migrated to the same position, indicating that both native enzymes are composed of subunits which could not be differentiated from each other by these procedures. The molecular weight of both fumarases was estimated to be 200, 000 by sucrose density gradient centrifugation and molecular sieve chromatography with Sephadex G-200. A subunit cross-linking experiment using glutaraldehyde revealed that both native enzymes were composed of four identical subunits. The amino acid composition of the cytosolic furnarase was shown to be very similar to that of the mitochondrial one by amino acid analysis. From the data obtained by amino acid analysis, the molecular weights of both native enzymes were calculated to be about 195, 000. Kinetic constants such as the apparent Km, the optimal pH and the specific activity of the cytosolic fumarase were quite similar to those of the mitochondrial enzyme. Furthermore, these two fumarases could not be differentiated from each other by immunochemical techniques, since a single precipitin band was formed between the rabbit antiserum against the cytosolic fumarase and the cytosolic or mitochon-drial fumarase. In addition, these precipitin bands fused completely with each other on the Ouchterlony double immunodiffusion test. These results may suggest that the fumarases located in the cytosolic and mito-chondrial fractions of the rat liver cell may be products of the same nuclear gene, and also that the structures of these two mature fumarases are very similar, if not identical.
Development Of Epid-Based Real Time Dose Verification For Dynamic Imrt (2011)

An electronic portal image device (EPID) has become a method of patient-specific IMRT dose verification for radiotherapy. Research studies have focused on pre and post-treatment verification, however, there are currently no interventional procedures using EPID dosimetry that measure the dose in real time as a mechanism to ensure that overdoses do not occur and underdoses are detected as soon as is practically possible. As a result, an EPID-based real time dose verification system for dynamic IMRT was developed and was implemented with MATLAB/Simulink. The EPID image acquisition was set to continuous acquisition mode at 1.4 images per second. The system defined the time constraint gap, or execution gap at the image acquisition time, so that every calculation must be completed before the next image capture is completed. In addition, the &lt;=-evaluation method was used for dose comparison, with two types of comparison processes; individual image and cumulative dose comparison monitored. The outputs of the system are the &lt;=-map, the percent of &lt;=&lt;1, and mean-&lt;= versus time, all in real time. Two strategies were used to test the system, including an error detection test and a clinical data test. The system can monitor the actual dose delivery compared with the treatment plan data or previous treatment dose delivery that means a radiation therapist is able to switch off the machine when the error is detected.
Type 17 CD8+ T cells display enhanced antitumor immunity (2009)

Interleukin-17 (IL-17)-secreting CD8(+) T cells have been described, but they have not been thoroughly studied and they do not have a known role in cancer immunotherapy. We skewed CD8(+) T cells to secrete IL-17 through priming in Th17-polarizing conditions. IL-17-producing CD8(+) T cells demonstrated reduced expression of Eomes and diminished cytolytic differentiation in vitro. However, after adoptive transfer, these cells converted to interferon-gamma-producing effector cells and mediated regression of large, established tumors. This improved antitumor immunity was associated with increased expression of IL-7R-alpha, decreased expression of killer cell lectin-like receptor G1, and enhanced persistence of the transferred cells. This report is the first description of a cancer therapy with IL-17-secreting CD8(+) T cells. These findings have implications for the improvement of CD8(+) T cell-based adoptive immunotherapy.
The herpes simplex virus amplicon: analyses of cis-acting replication functions. (1985)

Previous studies have shown that defective virus vectors (amplicons) derived from herpes simplex viruses could be efficiently propagated in virus stocks in the presence of trans-acting helper virus functions. The present study established that two separate cis-acting functions--a DNA replication origin and a cleavage/packaging signal--are required for amplicon propagation. Using deleted derivatives of cloned amplicons, we mapped one of the viral DNA replication origins (ori-2 or oriL) at coordinate 0.422 of the standard HSV-1 genome and at an equivalent position within the HSV-2 genome.
Avidity Determinations for Haemophilus influenzae Type b Anti-Polyribosylribitol Phosphate Antibodies (2005)

Determination of antibody avidity measurements can be difficult in human serum depending on the population evaluated. We evaluated three approaches for the determination of antibody avidity for immunoglobulin G (IgG). These approaches were (i) elution of bound antibody with increasing concentrations of a chaotropic agent using a single serum dilution, (ii) binding interference of multiple serum dilutions by a single concentration of a chaotrope, and (iii) elution of multiple serum dilutions by a single concentration of a chaotrope. Parameters that affect the determination of avidity measurements and their limitations were evaluated with pre- and post-Haemophilus influenzae type b conjugate vaccination sera (n=89). We determined that elution of low-avidity antibodies present in multiple dilutions of the serum sample by a single concentration of a chaotrope (0.15 M sodium thiocyanate [NaSCN]) was optimal for the determination of avidity measurements throughout a wide range of IgG concentrations (0.94 to 304.6 microg/ml). The percent reduction in concentration as determined by the elution assay with 0.15 M NaSCN correlated highly (r=0.84) with weighted averages obtained by an elution assay with multiple solutions of NaSCN. The correlation (r=0.57) between elution and binding interference, when a single concentration of a chaotrope was used, was lower than the correlation between the two elution methods (r=0.84). We found that the serum dilution, the heterogeneity of the antibody population, and the concentration of the chaotrope were the primary variables affecting avidity determinations. In this study, we present multiple analysis methods depending on the methodology used. We also present the factors that affect the analysis of avidity determinations given the polyclonal nature of human sera. This experimental approach should benefit the evaluation of similar antibodies induced by other bacterial polysaccharide vaccines.
Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin. (1991)

The heparin-binding p30 protein amphoterin is proposed to mediate adhesive interactions of the advancing plasma membrane in migrating and differentiating cells. Since the NH2-terminal part of amphoterin is exceptionally rich in lysine residues, we have studied its interactions with plasminogen and tissue plasminogen activator (t-PA). On immunostaining of N18 neuroblastoma cells, amphoterin and t-PA showed a close co-localization in the filopodia of the leading membrane and in the substrate-attached material. In purified systems, both t-PA and plasminogen bound to immobilized amphoterin, and their binding was inhibited by the lysine analogue epsilon-aminocaproic acid. Plasminogen bound to immobilized amphoterin was activated by t-PA, and this resulted in effective degradation of the immobilized amphoterin. Correspondingly, amphoterin-bound t-PA activated plasminogen. In solution amphoterin accelerated t-PA-catalyzed plasminogen activation maximally 46-fold. The results indicate that t-PA and plasminogen form through their lysine-binding sites a complex with amphoterin, which results in acceleration of plasminogen activation and effective degradation of amphoterin. We suggest that local acceleration of t-PA-catalyzed plasminogen activation by amphoterin at the leading membrane enhances the penetration of growing cytoplasmic processes through extracellular materials during cell migration, differentiation and regeneration. The amphoterin-mediated adhesion at the leading membrane may be transient in nature, because the protein also enhances its own breakdown by accelerating t-PA-catalyzed plasminogen activation.
Increased expression of the multidrug efflux genes acrAB occurs during slow growth of Escherichia coli (2002)

Intrinsic antimicrobial resistance of Escherichia coli is elicited by the gene products of the multidrug efflux acrAB-tolC operon.In this paper, we have shown that acrAB is regulated as a function of the growth rate of E. coli during growth in batch and chemostat culture.In chemostat culture, expression of acrAB is inversely related to growth rate irrespective of the limiting nutrient.The level of expression of acrAB is greater under glucose limitation compared with either iron or nitrogen limitation.Increase in expression of acrAB confers a greater resistance to ciprofloxacin, and the implications for a clinical situation are discussed.Slow growth rate regulation of acrAB transcription does not require the presence of the stationary-phase sigma factor.A putative gearbox consensus sequence was identified at the 310 region of the acrAB promoter.
An Assisted Photography Framework to Help Visually Impaired Users Properly Aim a Camera (2014)

We propose an assisted photography framework to help visually impaired users properly aim a camera and evaluate our implementation in the context of documenting public transportation accessibility. Our framework integrates user interaction during the image capturing process to help users take better pictures in real time. We use an image composition model to evaluate picture quality and suggest providing audiovisual feedback to improve users’ aiming position. With our particular framework implementation, blind participants were able to take pictures of similar quality to those taken by low vision participants without assistance. Likewise, our system helped low vision participants take pictures as good as those taken by fully sighted users. Our results also show a positive trend in favor of spoken directions to assist visually impaired users in comparison to tone and silent feedback. Positive usefulness ratings provided by full vision users further suggest that assisted photography has universal appeal.
Cigarette Smoking-induced Changes in the Number and Differentiated State of Pulmonary Dendritic Cells/ Langerhans Cells (1989)

To evaluate the effect of cigarette smoking on the number, distribution, and differentiated state of dendritic cells (DC) and Langerhans cells (LC) in the human lung, we have quantitated the number of these cells present in the bronchioles and alveolar parenchyma of lung tissue from nonsmokers and cigarette smokers using anti-CD1 monoclonal antibodies which react preferentially with DC (M241) and LC (T6). M241+ DC were found in the bronchiolar submucosa and alveolar parenchyma of nonsmokers; T6+ LC were present within the bronchiolar epithelium. Cigarette smoking was associated with a twofold increase in the total number of cells of DC/LC lineage and a 30-fold increase in the number of T6+ cells, many of which contained Birbeck granules (LC), present in the alveolar parenchyma. Most LC found in the parenchyma of smokers were observed in close association with areas of alveolar type II pneumocyte hyperplasia. Cigarette smoking did not change the number of differentiated state of cells of DC/LC lineage within the bronchioles. Both DC and LC are present in the human lung. Cigarette smoking has an important effect on the number, distribution, and differentiated state of these cells, which may explain why most adult patients who develop Langerhans cell granulomatosis are smokers.
Adversarial Learning for Neural Dialogue Generation (2017)

In this paper, drawing intuition from the Turing test, we propose using adversarial training for open-domain dialogue generation: the system is trained to produce sequences that are indistinguishable from human-generated dialogue utterances. We cast the task as a reinforcement learning (RL) problem where we jointly train two systems, a generative model to produce response sequences, and a discriminator-analagous to the human evaluator in the Turing test-to distinguish between the human-generated dialogues and the machine-generated ones. The outputs from the discriminator are then used as rewards for the generative model, pushing the system to generate dialogues that mostly resemble human dialogues.
Nanobelts of the dielectric material Ge3N4 (2001)

Ge 3 N 4 nanobelts 30–300 nm in width were synthesized by thermal reduction of a mixed Ge+SiO2 powder in NH3 atmosphere. These nanobelts were studied by high-resolution transmission electron microscope equipped with an x-ray energy dispersive spectrometer. In these synthesized nanobelts, the existence of α and β phases of Ge3N4 was identified. The α phase exhibiting slight difference from an ideal α-Ge3N4 phase was also found in the present Ge3N4 material. The mechanism of formation of the Ge3N4 nanobelts is discussed.
Enhanced Expression of the Type II Transforming Growth Factor-β Receptor Is Associated with Decreased Survival in Human Pancreatic Cancer (1999)

Transforming growth factor-betas (TGF-betas) bind to the type II TGF-beta receptor (TbetaRII), which then heterodimerizes with the type I TGF-beta receptor (TbetaRI), thereby initiating a signaling cascade. TGF-betas are overexpressed in pancreatic cancer, and this overexpression is associated with more aggressive disease. Although TbetaRII also is overexpressed in pancreatic ductal adenocarcinoma cells in vivo, the biologic significance of this overexpression is not completely known. Therefore in this study, we characterized TbetaRII expression by Northern blot analysis in 32 normal and 42 cancerous pancreatic tissues and correlated the survival of the cancer patients with TbetaRII messenger RNA (mRNA) levels. Northern blot analysis revealed that, by comparison with the normal controls, TbetaRII expression was increased in 19 (45%) of 42 cancer samples. Densitometric analysis of all the pancreatic tissues revealed a 3.4-fold increase (p < 0.01) in TbetaRII mRNA levels in the cancer tissues by comparison with normal controls. There was a strong correlation between the expression of TbetaRII and the levels of two invasion-promoting genes, plasminogen-activator-inhibitor-1 (PAI-1) and matrix-metalloproteinase-9 (MMP9). Log-rank analysis of the Kaplan-Meier survival curves indicated that patients whose tumors overexpressed TbetaRII had a significantly shorter survival period than did patients whose cancers expressed low levels of TbetaRII. It is suggested that TbetaRII overexpression may be a marker that correlates with disease progression in pancreatic ductal adenocarcinoma.
Tumor-targeting, enzyme-activated nanoparticles for simultaneous cancer diagnosis and photodynamic therapy (2015)

Specific targeting towards tumors and the on-site activation of photosensitizers to diagnose tumors and reduce side effects for patients are currently the main challenges for photodynamic therapy (PDT) in the clinic. Herein, uniform diiodostyryl bodipy conjugated hyaluronic acid nanoparticles (DBHA-NPs) were successfully synthesized. The evaluation of their PDT effect at both a cellular level and in animal models of tumor-bearing mice shows that the DBHA-NPs present a remarkable suppression of tumorous growth due to their specific targeting and enhanced permeability and retention (EPR) effect. More importantly, the enzyme-activated "self-assembly and disaggregation" behavior in tumors can lead to the on-site activation of DBHA-NPs, which can diagnose the tumor exactly and reduce the side effects for patients significantly. These findings confirm that DBHA-NPs have significant potential for photodynamically activated cancer theranostics in a clinical setting.
Lipase‐catalyzed triglyceride hydrolysis in organic solvent (1991)

An investigation of lipases from Rhizomucor miehei , Candida rug osa and porcine pancreas revealed that these enzymes hydrolyzed triglycerides in an organic solvent system. The presence of secondary amines, i.e. , diethylamine, N ‐methylbutylamine, or the tertiary amine, Methylamine, greatly increased the extent of hydrolysis. The lipolysis of tallow took place under mild conditions, e.g. , room temperature, moderate shaking and within 20 hr. At 45°C, complete hydrolysis of tallow was obtained in 6 hr. Vegetable oils and a fish oil (cod liver oil) were also hydrolyzed at 20°C by R. miehei lipase in the presence of iV‐methylbutylamine for 20 hr. The lipases were recovered for reuse with some loss of activity. Optimum yields of free fatty acids were obtained by using R. miehei lipase as catalyst.
Chemotactic activity on mononuclear cells in the cerebrospinal fluid of patients with viral meningitis is mediated by interferon‐γ inducible protein‐10 and monocyte chemotactic protein‐1 (1997)

In viral meningitis the inflammatory response involves activated T cells and monocytes which are recruited into the subarachnoid space. To identify the chemotactic signals attracting the cells to the site of infection in the meninges, we measured the levels of two CXC chemokines, interferon-gamma (IFN-gamma) inducible protein (IP)-10 and monokine induced by IFN-gamma, four CC chemokines, monocyte chemotactic protein (MCP)-1, RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, as well as the cytokines interleukin (IL)-15 and IL-16 in the cerebrospinal fluid (CSF) of patients suffering from viral meningitis. The results point to an involvement of two chemokines, MCP-1 and IP-10, since (1) unlike the other cytokines, MCP-1 and IP-10 were present in 97% and 79% of the CSF, respectively, at concentrations sufficient to induce chemotaxis of mononuclear cells; (2) more than 90% of the CSF of viral meningitis induced chemotaxis of peripheral blood mononuclear cells (PBMC) and all of them induced chemotaxis of activated T cells, and (3) the CSF-mediated chemotaxis of PBMC was inhibited by anti-MCP-1 antibodies and chemotaxis of activated T cells was abolished by the combination of anti-MCP-1 and anti-IP-10 antibodies. Our data provide evidence that MCP-1 and IP-10 lead to accumulation of activated T cells and monocytes in the CSF compartment in viral meningitis.
Protease‐Triggered Unveiling of Bioactive Nanoparticles (2008)

The ability to reveal bioactive domains on the surface of nanoparticles in response to microenvironmental cues in tumors could provide a powerful means for targeting their activity. The feasibility of such a design is demonstrated by veiling nanoparticles with protease-removable polymer coatings (see image). Multimodal visualization and quantification of this model system establishes the utility of these coatings to improve nanoparticle delivery and direct the unveiling of bioactive surface groups in solid tumors.
Isolation of a rearranged human transforming gene following transfection of Kaposi sarcoma DNA. (1987)

By transfecting high molecular weight DNA from a Kaposi sarcoma lesion into murine NIH 3T3 cells, we have identified and molecularly cloned a set of human DNA sequences capable of inducing focus formation, growth in agar, and tumorigenicity in these cells. The human DNA sequences present in primary, secondary, and tertiary NIH 3T3 transformants encompass about 32 kilobases (kb) and contain four rearrangements with respect to normal human DNA and a portion of the c-fms protooncogene (FMS in human gene nomenclature). However, the minimal transforming region (6.6 kb) identified in our cloned DNA borders on the c-fms DNA region but does not contain c-fms coding sequences. The fms sequences are also not represented in the two transcripts (approximately equal to 1.2 and 3.5 kb) detected in NIH 3T3 transformants; however, they might provide elements regulating expression. Hybridization to several known oncogene probes and preliminary sequencing data indicate that we have identified a previously unrecognized "activated" oncogene. Since the rearrangements present in our cloned DNA sequences are not detectable in the original Kaposi tumor DNA used for transfection, it is possible that this oncogene was generated during gene transfer.
Structural Alerts for Toxicity (2010)

Abstract This chapter summarizes structural alerts where there is a significant weight of evidence that their incorporation into a drug candidate molecule is likely to result in a higher than average incidence of attrition due to adverse safety/or toxicity findings. The mechanism of formation of reactive metabolites from each structural alert is summarized. The structure–toxicity relationships and the boundary of definition for each structural alert are discussed. The benefits of low exposure and alternative routes of metabolism are highlighted along with screening methods to manage the risks associated with structural alerts.