gebhart/patrepeval huggingface dataset:
Topical Hazard Evaluation Program of Candidate Insect Pepellents, May 1976 - April 1980. (1980)

Preliminary hazard evaluations of the above candidate repellent compounds were performed by means of laboratory animal studies using rats, rabbits and guinea pigs. Compounds AI3-70771, 37393a, 37395a, 37417a, 37414a, 37430a, 37468a, 37476, 37500, and 37487a caused moderate to severe eye irritations, and were not approved for further testing. Compounds AI3-37428a, 37485a, 26661c, 37461a, 37488a, 37494a, 37505a, 37507a, and 37510a caused moderate to severe primary skin irritations, and also were not approved for further testing. Additionally, compounds AI3-37173a, 37175a, 37412a, 37422a, and 37431a caused a phototoxic reaction, and were rejected for further study. The following compounds were judged sufficiently nontoxic to be approved for further study as candidate repellents: AI3-36580, 70735aGa, 20873cGc, 30005aGc, 36312Gb, 70772, 37171a, 37172a, 37178a, 37181a, 37184a, 37187a, 37133a, and 37415a. (Author)
Evolution of a Simian Immunodeficiency Virus Pathogen (1998)

Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculated rhesus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-kappaB binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3' half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5' half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU.
Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma (2015)

Background. Glioblastoma (GBM) is the most common and aggressive form of brain cancer. Our previous studies demonstrated that combined inhibition of HDAC and KDM1A increases apoptotic cell death in vitro. However, whether this combination also increases death of the glioma stem cell (GSC) population or has an effect in vivo is yet to be determined. Therefore, we evaluated the translational potential of combined HDAC and KDM1A inhibition on patient-derived GSCs and xenograft GBM mouse models. We also investigated the changes in transcriptional programing induced by the combination in an effort to understand the induced molecular mechanisms of GBM cell death.
Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras (2001)

Adenocarcinoma of the lung is the most common form of lung cancer, but the cell of origin and the stages of progression of this tumor type are not well understood. We have developed a new model of lung adenocarcinoma in mice harboring a conditionally activatable allele of oncogenic K-ras. Here we show that the use of a recombinant adenovirus expressing Cre recombinase (AdenoCre) to induce K-ras G12D expression in the lungs of mice allows control of the timing and multiplicity of tumor initiation. Through the ability to synchronize tumor initiation in these mice, we have been able to characterize the stages of tumor progression. Of particular significance, this system has led to the identification of a new cell type contributing to the development of pulmonary adenocarcinoma.
Integrated analysis of the genome and the transcriptome by FANTOM (2004)

The key to reliable annotation of a mammalian genome is broad characterisation of the transcriptional output, the transcriptome. FANTOM, the functional annotation of mouse cDNA, is a large-scale analysis of both the genome and the transcriptome of the mouse. In the early days of this work, the transcripts were characterised using our sophisticated methods. After the timely release of the first draft of mouse genome sequences, interesting information was obtained by its integration with these one-by-one annotations. Moreover, each transcript included its expression profile. Here, the two integrated annotation methods used by FANTOM are reviewed: one-by-one and categorised. One-by-one annotation refers to naming carried out based on well-known transcripts or its fragments using the top-down-style pipeline developed mostly by the FANTOM project. Categorised annotation, which refers to transcript grouping, not only helps naming of unknown transcripts, but will be the most utilised method for integration of the genome and the transcriptome from now on.
Bluetooth technology and its implementation in sensing devices (2001)

Bluetooth Wireless technology is the world's new short range RF transmission standard for small form factor, low cost, and short-range radio link between portable and desktop devices. This technology does not replace Wireless LANs rather it compliments them. Bluetooth wireless technology has many advantages over other Wireless LAN technologies, which makes it attractive to many applications. One such application is in the area of sensors and gauges on-board ships and submarines. If these are connected wirelessly, a huge amount of cables are eliminated and more user mobility is gained. This thesis studies the theories and principles of Bluetooth technology and discusses the approaches of connecting Bluetooth to sensors and gauges. Some of the Bluetooth products available in the market were acquired for testing and evaluation. In the course of the study, it was found that the technology was not mainly developed with sensor and gauge applications in mind. However, integrating sensors with Bluetooth modules can be achieved by one of two approaches. One approach requires an expensive Development Kit and is limited to manufacturers integrating Bluetooth technology into their sensor products in compliance with Bluetooth Specifications. The other inexpensive approach requires custom circuit designing and program coding and is preferred by university researchers.
All Autophosphorylation Sites of Epidermal Growth Factor (EGF) Receptor and HER2/neu Are Located in Their Carboxyl-terminal Tails (1989)

Activation of the epidermal growth factor (EGF) receptor kinase leads to autophosphorylation and to the phosphorylation of various cellular substrates. The three known autophosphorylation sites of EGF receptor are located at the carboxyl-terminal tail where they probably act to compete with and thus modulate substrate phosphorylation. Mutational analysis and microsequencing techniques have been used to localize and identify new autophosphorylation site(s) of the EGF receptor. We have compared the phosphopeptide maps of human EGF receptor, and two deletion mutants lacking 63 and 126 amino acids from the carboxyl-terminal tail with the phosphopeptide maps of HER/neu and a chimeric EGF receptor containing the carboxyl-terminal tail of HER2/neu. HER2/neu is highly homologous to the EGF receptor, and it probably functions as a growth factor receptor for as yet unidentified growth factor. On the basis of this analysis, we have concluded that all autophosphorylation sites of EGF receptor and HER2/neu are located in their carboxyl-terminal tails. Utilizing the EGF receptors with carboxyl-terminal deletions, we were also able to identify tyr1086 as an additional autophosphorylation site of EGF receptor. Direct microsequencing of a phosphorylated tryptic peptide from the human EGF receptor confirmed this assignment.
Drug Absorption in the Management of Congestive Heart Failure: Loop Diuretics (2003)

Congestive heart failure is a disease state distinguished by the regular presence of both renal and hepatic abnormalities in drug handling. One such abnormality involves flaws in the process of drug absorption. In most instances, congestive heart failure-related abnormalities in drug absorption are of inconsequential significance. However, this is not the case with loop diuretics. Loop diuretic action ordinarily tracks the rate and extent of absorption if a sufficient amount of diuretic has been given to exceed the threshold for diuretic effect. In congestive heart failure, both the rate and absolute amount of loop diuretic absorbed can be reduced as a function of the heart failure state itself. In this setting, drug dissolution characteristics can assume added significance. Furosemide is the loop diuretic with the widest intra- and interpatient variability of absorption. Alternatively, the loop diuretic torsemide is rapidly and fairly completely absorbed independent of the heart failure state. This pattern of absorption establishes it as the preferred loop diuretic in the otherwise diuretic-resistant heart failure patient. However, the exact role of torsemide in the outpatient management of congestive heart failure remains to be determined.
Neurotrophic Factors: Important Regulators of Nociceptive Function (2001)

Neurotrophic factors have an established developmental role in regulating the survival and specification of sensory neurons. However, these factors continue to exert an important influence on sensory neurons throughout the postnatal period and into adult life. In adulthood, approximately one-half of nociceptors are dependent on nerve growth factor (NGF) for trophic support, whereas the other half are sensitive to glial cell line-derived neurotrophic factor (GDNF). It is now known that many chronic pain states are maintained by widespread changes in the anatomy, neurochemistry, and function of the sensory nervous system both at the level of the primary sensory neuron and the dorsal horn of the spinal cord. Trophic factors appear to orchestrate many of these dynamic changes. This review highlights some of the key roles played by these molecules and in particular the role of NGF in the peripheral sensitization of nociceptors and brain-derived neurotrophic factor (BDNF) as a central pain modulator.
The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability. (1995)

Genomic silencing is a fundamental mechanism of transcriptional regulation, yet little is known about conserved mechanisms of silencing. We report here the discovery of four Saccharomyces cerevisiae homologs of the SIR2 silencing gene (HSTs), as well as conservation of this gene family from bacteria to mammals. At least three HST genes can function in silencing; HST1 overexpression restores transcriptional silencing to a sir2 mutant and hst3 hst4 double mutants are defective in telomeric silencing. In addition, HST3 and HST4 together contribute to proper cell cycle progression, radiation resistance, and genomic stability, establishing new connections between silencing and these fundamental cellular processes.
Improved Understanding of the Bacterial Vaginal Microbiota of Women before and after Probiotic Instillation (2003)

The vaginal bacterial microbiota of 19 premenopausal women was examined by PCR-denaturing gradient gel electrophoresis (DGGE) and sequencing of the V2-V3 region of the 16S rRNA gene. Ten of the women were studied further to investigate the effect and persistence of vaginally inserted capsules containing viable lactobacilli. PCR-DGGE indicated that most subjects had a microbiota represented by one to three dominant DNA fragments. Analysis of these fragments revealed that 79% of the women possessed sequences with high levels of similarity to Lactobacillus species sequences. Sequences homologous to Lactobacillus iners sequences were the most common and were detected in 42% of the women tested. Alteration of the vaginal microbiota could be detected by PCR-DGGE in several women after the instillation of lactobacilli. Additionally, randomly amplified polymorphic DNA analysis of lactobacilli isolated from selective media demonstrated that the exogenous strains could be detected for up to 21 days in some subjects. This study demonstrates that non-culture-based techniques, such as PCR-DGGE, are useful adjuncts for studies of the vaginal microbiota.
Initiation of homologous recombination at DNA nicks (2018)

Discontinuities in only a single strand of the DNA duplex occur frequently, as a result of DNA damage or as intermediates in essential nuclear processes and DNA repair. Nicks are the simplest of these lesions: they carry clean ends bearing 3'-hydroxyl groups that can undergo ligation or prime new DNA synthesis. In contrast, single-strand breaks also interrupt only one DNA strand, but they carry damaged ends that require clean-up before subsequent steps in repair. Despite their apparent simplicity, nicks can have significant consequences for genome stability. The availability of enzymes that can introduce a nick almost anywhere in a large genome now makes it possible to systematically analyze repair of nicks. Recent experiments demonstrate that nicks can initiate recombination via pathways distinct from those active at double-strand breaks (DSBs). Recombination at targeted DNA nicks can be very efficient, and because nicks are intrinsically less mutagenic than DSBs, nick-initiated gene correction is useful for genome engineering and gene therapy. This review revisits some physiological examples of recombination at nicks, and outlines experiments that have demonstrated that nicks initiate homology-directed repair by distinctive pathways, emphasizing research that has contributed to our current mechanistic understanding of recombination at nicks in mammalian cells.
Chromosome-mediated gene transfer of multidrug resistance. (1986)

Multidrug resistance can be transferred from drug-resistant LZ Chinese hamster cells to drug-susceptible mouse LTA cells by chromosome-mediated gene transfer. Analysis of genomic DNA demonstrated the transfer of multiple copies of a DNA domain which is amplified in the donor multidrug-resistant cells. The transfer of 10 to 15 copies of the Chinese hamster gene was sufficient to produce a multidrug-resistant phenotype. Chromosome transferents exhibited overexpression of an mRNA of approximately 5 kilobases which has previously been demonstrated to be encoded by the amplified DNA domain of the donor LZ cells. Phenotypic analysis of individual clones selected in adriamycin showed the resistance to be pleiotropic. All clones tested demonstrated similar levels of cross-resistance to the drugs daunorubicin and colchicine. These results indicate that the DNA sequences transferred confer the complete multidrug-resistant phenotype on recipient cells and suggest that multidrug resistance is due to overexpression of the protein encoded by the 5-kilobase mRNA.
Virtual memory transaction management (1984)

In this paper we examine the consequences of an operating system providing transaction management in an environment where files are bound into a user's address space. The discussion focuses on inherent limitations in providing concurrency control and crash recovery services in this environment and on hardware extensions needed to overcome these deficiencies.
Identification of amino acid residues involved in substrate specificity of plant acyl-ACP thioesterases using a bioinformatics-guided approach. (2007)

Four of six putative specificity determining positions in plant TEs, identified with the use of CPDL, were validated experimentally; a novel colorimetric screen that discriminates between active and inactive TEs is also presented.
ARTIFICIAL MAINTENANCE MEDIA FOR CELL AND ORGAN CULTIVATION (1939)

Experiments have been described in which organs cultivated in the Lindbergh apparatus have been kept alive in artificial media for periods ranging from 3 days to 3 weeks, with life continuing in portions of some glands for from 35 to 62 days. The media used varied in composition from very simple and inexpensive ones in which some serum was used to a rather complex medium containing only that negligible amount of serum that is necessary as a solvent for vitamin A. The experiments performed demonstrate that artificial media can be used for organ cultivation, thus making it possible to study the behavior of human organs; to control the composition of the media at will; and to reduce the cost of experimentation.
The Horcrux Protocol: A Method for Decentralized Biometric-based Self-sovereign Identity (2018)

Most user authentication methods and identity proving systems rely on a centralized database. Such information storage presents a single point of compromise from a security perspective. If this system is compromised it poses a direct threat to users digital identities. This paper proposes a decentralized authentication method, called the Horcrux protocol, in which there is no such single point of compromise. The protocol relies on decentralized identifiers (DIDs) under development by the W3C Verifiable Claims Community Group and the concept of self-sovereign identity. To accomplish this, we propose specification and implementation of a decentralized biometric credential storage option via blockchains using DIDs and DID documents within the IEEE 2410-2017 Biometric Open Protocol Standard (BOPS).
Endothelial leukocyte adhesion molecule-1 mediates antigen-induced acute airway inflammation and late-phase airway obstruction in monkeys. (1991)

This study examines the role of endothelial leukocyte adhesion molecule-1 (ELAM-1) in the development of the acute airway inflammation (cell influx) and late-phase airway obstruction in a primate model of extrinsic asthma. In animals sensitive to antigen, a single inhalation exposure induced the rapid expression of ELAM-1 (6 h) exclusively on vascular endothelium that correlated with the influx of neutrophils into the lungs and the onset of late-phase airway obstruction. In contrast, basal levels of ICAM-1 was constitutively expressed on vascular endothelium and airway epithelium before antigen challenge. After the single antigen exposure, changes in ICAM-1 expression did not correlate with neutrophil influx or the change in airway caliber. This was confirmed by showing that pretreatment with a monoclonal antibody to ICAM-1 did not inhibit the acute influx of neutrophils associated with late-phase airway obstruction, whereas a monoclonal antibody to ELAM-1 blocked both the influx of neutrophils and the late-phase airway obstruction. This study demonstrates a functional role for ELAM-1 in the development of acute airway inflammation in vivo. We conclude that, in primates, the late-phase response is the result of an ELAM-1 dependent influx of neutrophils. Therefore, the regulation of ELAM-1 expression may provide a novel approach to controlling the acute inflammatory response, and thereby, affecting airway function associated with inflammatory disorders, including asthma.
Use of model cell lines to study the biosynthesis and biological role of cancer-associated sialosyl-Tn antigen. (1994)

Sialosyl-Tn (STn) is a mucin-associated carbohydrate antigen that is not expressed by most normal epithelial cells but becomes expressed in several types of adenocarcinomas, where it is often associated with a poor prognosis. Little is known about the regulation of the STn phenotype in tumor cells and the immune response to STn antigen. In the present study, we established clonal cell lines in which virtually all of the cells were STn positive (designated LS-C) or STn negative (designated LS-B). These two cell lines, derived from a single parental cell line, LS174T, have the same total protein electrophoretic profiles but carry markedly different oligosaccharide structures on their mucin; the mucin from LS-C cells has only the Tn and STn structures, whereas LS-B cell mucin lacks these simple structures but carries more complex oligosaccharides. These results indicate that lack of STn expression by cells can be due to the lack of STn synthesis rather than inaccessibility of antibodies to bind to STn by steric hindrance. Both clones were similar in their growth rates, response to gamma-interferon, and sensitivity to lysis by lymphokine-activated killer cells. These cells may be important models for understanding the regulation of glycosylation at the cellular level and for further studies of tumor biology and immune response to STn antigen.
Inverse Scattering Solutions by a Sinc Basis, Multiple Source, Moment Method -- Part III: Fast Algorithms (1984)

Solving the inverse scattering problem for the Helmholtz wave equation without employing the Born or Rytov approximations is a challenging problem, but some slow iterative methods have been proposed. One such method suggested by us is based on solving systems of nonlinear algebraic equations that are derived by applying the method of moments to a sinc basis function expansion of the fields and scattering potential. In the past, we have solved these equations for a 2-D object of n by n pixels in a time proportional to n 5 . In the present paper, we demonstrate a new method based on FFT convolution and the concept of backprojection which solves these equations in time proportional to n 3 • log(n). Several numerical examples are given for images up to 7 by 7 pixels in size. Analogous algorithms to solve the Riccati wave equation in n 3 • log(n) time are also suggested, but not verified. A method is suggested for interpolating measurements from one detector geometry to a new perturbed detector geometry whose measurement points fall on a FFT accessible, rectangular grid and thereby render many detector geometrics compatible for use by our fast methods.
Lymphocyte subpopulations in patients with primary fibromyalgia. (1994)

Our results suggest a defect in T cell activation in patients with FM.