gebhart/patrepeval huggingface dataset:
pAd5-Blue: Direct Ligation System for Engineering Recombinant Adenovirus Constructs (2001)

We have engineered a new vector that makes use of direct ligation for the generation of replication-defective recombinant adenovirus constructs. In the pAd5-Blue vector, unique yet common restriction endonuclease sites exist, that allow cloning in a directional manner of a gene of interest under control of a cytomegalovirus promoter, upstream of a simian virus 40 polyadenylation signal. The insertion of the new gene replaces the beta-galactosidase alpha gene fragment in the pAd5-Blue vector, allowing the identification of recombinants in bacterial culture by the selection of white colonies. Plasmid DNA from white colonies is digested with PacI and transfected into 293 cells, resulting in the generation of a homogenous population of adenovirus containing the gene of interest. The pAd5-Blue vector system does not rely on recombination either in mammalian or bacterial cells. Furthermore, because of compatible overhangs, the variety of restriction endonucleases that can be used to generate the inserted gene gives flexibility to the process for greater ease of use. The system is quick and straightforward, allowing the generation of recombinant adenoviruses within three weeks of obtaining an appropriate insert. This new vector should greatly enhance the ease and speed with which new recombinant adenovirus constructs can be made.
Iterative algorithms for twin-image elimination in in-line holography using finite-support constraints (1993)

The quality of reconstructed images from in-line holograms can be seriously degraded by the linear superposition of twin images having the same information but different foci. Starting from the reconstructed field at the real image plane, we make use of the uncontaminated information contained in the out-of-focus wave (virtual image) outside the in-focus wave (real image) support, together with a finite-support constraint, to form an iterative procedure for twin-image elimination. This algorithm can reconstruct complex objects, provided that they are not recorded in very near-field conditions. For real objects additional constraints can be imposed, extending the algorithm application to very near-field conditions. The algorithm’s convergence properties are studied in both cases, and some examples are shown.
Antitumor effects of an immunotoxin made with Pseudomonas exotoxin in a nude mouse model of human ovarian cancer. (1986)

An immunotoxin composed of Pseudomonas toxin coupled to an antibody to the human transferrin receptor was evaluated for its effect on ovarian cancer. In the tumor model employed, 60 million human ovarian cancer cells were injected into the peritoneal cavity of an immunodeficient nude mouse. By day 5, cancer cells were implanted and growing in small clusters throughout the peritoneal cavity. On days 5-8, 0.3-2 micrograms of immunotoxin was injected into the peritoneal cavity. Control mice died with malignant ascites at 34-58 days after the implantation of tumor cells, whereas immunotoxin-treated mice lived to 100 days or longer. Irrelevant immunotoxins or antibody alone had no antitumor activity. These findings suggest that intraperitoneal injection of immunotoxins may have a role in the treatment of ovarian cancer.
Knowledge Distillation for Small-footprint Highway Networks (2016)

Deep learning has significantly advanced state-of-the-art of speech recognition in the past few years. However, compared to conventional Gaussian mixture acoustic models, neural network models are usually much larger, and are therefore not very deployable in embedded devices. Previously, we investigated a compact highway deep neural network (HDNN) for acoustic modelling, which is a type of depth-gated feedforward neural network. We have shown that HDNN-based acoustic models can achieve comparable recognition accuracy with much smaller number of model parameters compared to plain deep neural network (DNN) acoustic models. In this paper, we push the boundary further by leveraging on the knowledge distillation technique that is also known as {\it teacher-student} training, i.e., we train the compact HDNN model with the supervision of a high accuracy cumbersome model. Furthermore, we also investigate sequence training and adaptation in the context of teacher-student training. Our experiments were performed on the AMI meeting speech recognition corpus. With this technique, we significantly improved the recognition accuracy of the HDNN acoustic model with less than 0.8 million parameters, and narrowed the gap between this model and the plain DNN with 30 million parameters.
Lymphocyte subpopulations infiltrating squamous carcinomas of the head and neck: Correlations with extent of tumor and prognosis (1986)

Because little is known about the mechanisms involved in local tumor-host immune reactions in squamous carcinoma of the head and neck, a study was undertaken to better characterize the types of immune cells present at the local tumor site and determine their relationship to tumor extent, systemic cellular immune parameters, and clinical outcome. In 40 untreated patients, lymphocyte subsets (LS) at the tumor-host interface were quantitated immunohistologically from serial sections of frozen tumor specimens and correlated with concurrently measured peripheral LS levels and in vitro lymphocyte reactivity to phytohemagglutinin (PHA). The majority of infiltrating lymphocytes were T cells with rare B or Leu 7 cells. Proportions of T4 and T8 were similar in peritumor stroma; however, T8 cells predominated tumor parenchyma. Stromal and parenchymal infiltration by LS were not related to peripheral blood LS levels, lymphocyte reactivity, or tumor site. However, parenchymal T11 and T4 cell infiltration was less in advanced primary tumors (T3, T4) than in early tumors (T1, T2) (P = 0.01, P = 0.067, respectively), as was peripheral lymphocyte reactivity to PHA (P = 0.013). Short-term disease-free interval and actuarial survival differed significantly--according to parenchymal T11 and T4 cell infiltration--and were not related to T8, Leu 7, and B-cell infiltration. The findings extend prior studies of lymphocytic infiltration in head and neck cancer and demonstrate the potential importance of differences in tumor stromal and parenchymal infiltration. Together with recent evidence that T4 cells are critical for lymphokine production and for the proliferation of cytotoxic effector cells, the current results suggest that T4 cells play a critical role in the local immune response in squamous carcinoma of the head and neck.
Lysosomal Membrane Permeabilization by Targeted Magnetic Nanoparticles in Alternating Magnetic Fields (2013)

Lysosomal death pathways are being explored as alternatives of overcoming cancer tumor resistance to traditional forms of treatment. Nanotechnologies that can selectively target and induce permeabilization of lysosomal compartments in cells could become powerful medical tools. Here we demonstrate that iron oxide magnetic nanoparticles (MNPs) targeted to the epidermal growth factor receptor (EGFR) can selectively induce lysosomal membrane permeabilization (LMP) in cancer cells overexpressing the EGFR under the action of an alternating magnetic field (AMF). LMP was observed to correlate with the production of reactive oxygen species (ROS) and a decrease in tumor cell viability. Confocal microscopy images showed an increase in the cytosolic activity of the lysosomal protease cathepsin B. These observations suggest the possibility of remotely triggering lysosomal death pathways in cancer cells through the administration of MNPs which target lysosomal internalization pathways and the application of AMFs.
982. The volatility of nitrates and nitrites of the alkali metals (1963)

C. J. Hardy and B. O. Field, J. Chem. Soc., 1963, 5130 DOI: 10.1039/JR9630005130
Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma (2003)

The full potential of a graft-versus-myeloma effect after allogeneic hematopoietic cell transplantation (HCT) for patients with multiple myeloma (MM) has not been realized because of excessive early transplantation-related mortality (TRM) with conventional HCT. Autologous HCTs have been characterized by almost universal disease recurrences. The current trial combined autologous HCT with subsequent nonmyeloablative allogeneic HCT to maintain the benefits of both approaches with acceptable toxicity. Fifty-four patients, 52 years of age (median; range, 29-71 years), with previously treated stage II or III MM (52% refractory or relapsed disease) were given melphalan 200 mg/m2 and autologous HC transplants. Regimen-related toxicities after autologous HCT were moderate with a median of 6 days of neutropenia, 7 days of hospitalization, and 1 death from infection. Forty to 229 days later (median, 62 days), 52 patients received a single fraction dose of 2 Gy total body irradiation and HC transplants from HLA-identical siblings with postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). Patients experienced medians of 0 days of hospitalization, neutropenia, and thrombocytopenia. Sustained engraftment was uniform. With a median follow-up of 552 days after allografting, overall survival is 78%. One patient (2%) died before day 100 from disease progression. Thirty-eight percent of patients developed acute graft-versus-host disease (GVHD; grade II in all but 4 cases) and 46% chronic GVHD requiring therapy. Tumor responses occurred slowly. Thus far, 57% of patients have achieved complete remissions and 26% have achieved partial remissions for an overall response of 83%. Despite being evaluated in elderly patients with MM, this 2-step approach has reduced the acute toxicities of allogeneic HCT while achieving potent antitumor activities.
A global reference for human genetic variation (2015)

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
The Measurement of Intra-abdominal Pressure as a Criterion for Abdominal Re-exploration (1984)

Acute elevation of intra-abdominal pressure above 30 mmHg caused oliguria in 11 postoperative patients. Operative re-exploration and decompression in seven patients resulted in immediate diuresis. Four patients who were not re-explored developed renal failure and died. If intra-abdominal pressure rises above 25 mmHg in the early postoperative period and is associated with oliguria and normal blood pressure and cardiac index, the patient should undergo re-exploration and decompression of the abdomen.
Expression and Function of Lysophosphatidic Acid Receptors in Cultured Rodent Microglial Cells (2001)

Microglia are the resident tissue macrophages of the central nervous system. They are rapidly activated by a variety of insults; and recently, receptors linked to cytoplasmic Ca(2+) signals have been implicated in such events. One potential class of receptors are those recognizing lysophosphatidic acid (LPA). LPA is a phospholipid signaling molecule that has been shown to cause multiple cellular responses, including increases in cytoplasmic calcium. We examined whether any of the known LPA receptor genes (lp(A1)/Edg2, lp(A2)/Edg4, and lp(A3)/Edg7) are expressed by cultured mouse or rat microglia. Reverse transcriptase-polymerase chain reaction indicated that mouse microglia predominantly expressed the lp(A1) gene, whereas rat microglia predominantly expressed lp(A3). Although LPA induced increases in the cytoplasmic Ca(2+) concentration in both microglial preparations, the responses differed substantially. The Ca(2+) signal in rat microglia occurred primarily through Ca(2+) influx via the plasma membrane, whereas the Ca(2+) signal in mouse microglia was due to release from intracellular stores. Only at high concentrations was an additional influx component recruited. Additionally, LPA induced increased metabolic activity in mouse (but not rat) microglial cells. Our findings provide evidence for functional LPA receptors on microglia. Thus, LPA might play an important role as a mediator of microglial activation in response to central nervous system injury.
Dynamic treatment effect (DTE) curves reveal the mode of action for standard and experimental cancer therapies (2015)

We present a method for estimating the empirical dynamic treatment effect (DTE) curves from tumor growth delay (TGD) studies. This improves on current common methods of TGD analysis, such as T/C ratio and doubling times, by providing a more detailed treatment effect and overcomes their lack of reproducibility. The methodology doesn't presuppose any prior form for the treatment effect dynamics and is shown to give consistent estimates with missing data. The method is illustrated by application to real data from TGD studies involving three types of therapy. Firstly, we demonstrate that radiotherapy induces a sharp peak in inhibition in a FaDu model. The height, duration and timing of the peak increase linearly with radiation dose. Second, we demonstrate that a combination of temozolomide and an experimental therapy in a glioma PDX model yields an effect, similar to an additive version of the DTE curves for the mono-therapies, except that there is a 30 day delay in peak inhibition. In the third study, we consider the DTE of anti-angiogenic therapy in glioma. We show that resulting DTE curves are flat. We discuss how features of the DTE curves should be interpreted and potentially used to improve therapy.
Phylogenetic Analysis of the Genus Bifidobacterium and Related Genera Based on 16S rDNA Sequences (1998)

The 16S rRNA gene sequences were determined for type strains of 21 Bifidobacterium species. A phylogenetic tree was constructed using the determined sequences and sequences from DNA databases, which contain the sequences of 11 type strains of Bifidobacterium species and 11 strains of related genera. All species of the genus Bifidobacterium and Gardnerella vaginalis ATCC 14018 belonged to a cluster phylogenetically distinct from the other genera. The cluster was divided into two subclusters: subcluster 1 composed of most species of Bifidobacterium and G. vaginalis, and subcluster 2 consisting of two species, B. denticolens and B. inopinatum; both of which were isolated from human dental caries. In the genus Bifidobacterium, four groups of species are known to be moderately to highly related by DNA-DNA hybridization. The four groups of species exhibited more than 99% similarity among their 16S rDNA sequences within each group. These results indicated that species with around 99% or more similarity in their 16S rDNA sequences should be confirmed for species identities.
Enhanced Gene Transfer to Mouse Dendritic Cells Using Adenoviral Vectors Coated with a Novel Adapter Molecule (2004)

Adenovirus (Ad)-mediated transduction of dendritic cells (DC) is inefficient because of the lack of the primary Ad receptor, CAR. DC infection with Ad targeted to the CD40 results in increased gene transfer. The current report describes further development of the CD40-targeting approach using an adapter molecule that bridges the fiber of the Ad5 to CD40 on mouse DC. The adapter molecule, CFm40L, consists of CAR fused to mouse CD40 ligand via a trimerization motif. A stable cell line that secretes CFm40L at high levels was generated. Gene transfer to mouse bone marrow-derived DC (mBMDC) using CFm40L-targeted Ad was over 4 orders of magnitude more efficient than that for the untargeted Ad5. Gene transfer was achieved to over 70% of the mBMDC compared to undetectable transduction using untargeted Ad5. In addition to dramatically enhanced gene transfer, the CFm40L-targeted Ad5 induced phenotypical maturation and upregulated IL-12 expression. Most importantly, the CFm40L-targeted Ad5 elicited specific immune response against a model antigen in vivo. The results of this study demonstrate that Ad-mediated gene transfer to DC can be significantly enhanced using nonnative transduction pathways, such the CD40 pathway, which may have important applications in genetic vaccination for cancer and infectious diseases.
Taxing Prizes and Awards: Proposed Amendments to Section 74 to Treat Meritorious Achievements Equitably (2017)

a World Cup, an Olympic medal, or a Paralympic medal is a meritorious achievement. 1 Elinor Ostrom, a professor who received a Nobel Prize in Economic Sciences, disproved the long-held idea that collectively-used natural resources "would be over-exploited and destroyed in the long-
Structure and function of apurinic/apyrimidinic endonucleases (1995)

The DNA of all species is constantly under threat from both endogenous and exogenous factors, which damage its chemical structure. Probably the most common lesion that arises in cellular DNA is the loss of a base to generate an abasic site, which is usually referred to as an apurinic or apyrimidinic (AP) site. Since these lesions are potentially both cytotoxic and mutagenic, cells of all organisms express dedicated repair enzymes, termed AP endonucleases, to counteract their damaging effects. Indeed, many organisms consider it necessary to express two or more of these lesion-specific endonucleases, underscoring the requirement that exists to remove AP sites for the maintenance of genome integrity and cell viability. Most AP endonucleases are very versatile enzymes, capable of performing numerous additional repair roles. In this article, we review the AP endonuclease class of repair enzymes, with emphasis on the evolutionary conservation of structural features, not only between prokaryotic and eukaryotic homologues, but also between these enzymes and the RNase H domain of one class of reverse transcriptase.
Vector development: A major obstacle in human gene therapy (1998)

Gene therapy has been proposed for a wide variety of human conditions including monogenic disorders, such as the haemoglobinopathies and immunodeficiency syndromes, cancer and many other diseases. Prerequisites for the success of this approach include the ability to deliver the therapeutic gene intact to the target cell, persistent levels of transgene expression sufficient to correct the disease phenotype, lack of unwanted side-effects associated with vector exposure or gene transfer and relative simplicity allowing the widespread use of this methodology. Although substantial progress has been made in animal models since the inception of genetic therapy in the early 1980s, significant obstacles remain for human therapy, most notably in the area of vector development. The first generation of gene therapy vectors has failed to overcome many of the biological hurdles cited above necessitating the development of alternate means of gene delivery and expression.
Interaction of African trypanosomes with the immune system (1984)

African trypanosomes cause disease in man and domestic animals. The parasites have the ability to escape immune control by two means: by antigenic variation of the surface glycoprotein coat so that waves of variant parasites arise and by inducing a general immunosuppression affecting immune responses to the parasite as well as to parasite-unrelated antigens. The cellular basis of the immune dysfunction will be discussed in relation to a mouse model system - it is the result of proliferative stimuli to T- or B-cells which then become refractory to selection by antigen and normal control signals. Recent experiments have focused on macrophages as important direct target cells for parasite action. We have obtained no evidence for a parasite derived mitogen acting directly on B- or T-cells. In vitro cell proliferation is associated with accessory cells and relates only to T-cells. During infection, macrophages become activated with changes in receptor expression and mediator release, so that there is, for example, spontaneous IL-1 release (with a role in T- and possibly in B-cell proliferation) and several-fold increases in PGE2 secretion, with its immunosuppressive activities. We also find parasitaemia-associated release of alpha-beta and gamma interferon by various cells which in turn influences immune function. The active parasite component is associated with parasite membranes, but its nature has not been further defined. We proposed that the macrophage changes provide a general pathway causing immune dysfunction associated with many infections, be they parasitic or caused by other invading organisms.
Role of pyocyanin in the acquisition of iron from transferrin (1986)

Pseudomonas aeruginosa produces a blue pigment called pyocyanin. In the presence of oxidizable substrates, bacteria reduce this pigment to a colorless product, leukopyocyanin. Pyocyanin can also be nonenzymatically reduced by NADH. Leukopyocyanin formed by cell- or NADH-mediated reduction nonenzymatically reduces oxygen or Fe(III). Pyocyanin-dependent iron reduction by whole bacterial cells was measured by the formation of the ferrous-ferrozine complex. In addition, leukopyocyanin reduced chelated Fe(III) including ferric iron in complex with transferrin, the serum iron-binding protein. High-pressure liquid chromatography was used to display the reductive removal of iron from transferrin and the accumulation of iron in the ferrous-ferrozine complex. Pyocyanin stimulated the accumulation of 55Fe from [55Fe]transferrin when it was added to bacteria incubated under low-oxygen conditions. Although bacteria grown in the presence of 100 microM FeCl3 reduced pyocyanin just as rapidly as iron-limited bacteria, these cells did not accumulate iron in the presence or absence of pyocyanin. Therefore, P. aeruginosa participates indiscriminantly in the reduction of pyocyanin, but soluble or available iron generated by the pyocyanin is taken up specifically by iron-limited bacteria.