gebhart/patrepeval huggingface dataset:
Single-molecule quantification of 5-hydroxymethylcytosine for diagnosis of blood and colon cancers (2017)

Single-molecule detection of 5hmC allows distinguishing between malignant and healthy tissue in clinically relevant and accessible tissue such as blood and colon. The presented method outperforms current commercially available quantification kits and may potentially be developed into a widely used, 5hmC quantification assay for research and clinical diagnostics. Furthermore, using this method, we confirm that 5hmC is a good molecular biomarker for diagnosing colon and various types of blood cancer.
Amphiphilic Indole Derivatives as Antimycobacterial Agents: Structure–Activity Relationships and Membrane Targeting Properties (2017)

Antibacterials that disrupt cell membrane function have the potential to eradicate "persister" organisms and delay the emergence of resistance. Here we report the antimycobacterial activities of 4-fluoro and 6-methoxyindoles bearing a cationic amphiphilic motif represented by a lipophilic n-octyl side chain at position 1 and a positively charged azepanyl or 1,4-dioxa-8-azaspiro[4.5]decane moiety at position 3. These analogues exhibited balanced profiles of potency (Mycobacterium bovis BCG, M tuberculosis H37Rv), selective activity, solubility, and metabolic stability. Bacteriological mechanism of action investigations on a representative analogue revealed cell membrane permeabilization and depolarization in M bovis BCG. These membrane-related changes preceded cell death indicating that the loss in membrane integrity was not an epiphenomenon. Bactericidal activity was observed against both growing and nongrowing mycobacterial cultures. The analogue also upregulated cell envelope stress-inducible promoters piniBAC and pclgR, implicating the involvement of envelope-related targets in its mode of action.
The immunosuppressant FTY720 down‐regulates sphingosine 1‐phosphate G protein‐coupled receptors (2004)

FTY720 is an immunosuppressant that reduces circulating levels of naïve lymphocytes by increasing their localization and sequestration in secondary lymphoid organs. It is considered to be an agonist for sphingosine 1-phosphate (S1P) G protein-coupled receptors (GPCRs) after phosphorylation at micromolar concentrations. We now describe its nonagonist and noncompetitive inhibitory activity at low nanomolar concentrations for types 1 and 5 S1P-GPCRs and of moderate potency for type 2 S1P-GPCRs. FTY720 blocks S1P signaling through S1P1,2,5 by inducing their internalization and intracellular partial degradation without affecting S1P3 or S1P4. S1P-R internalization is maximal several hours after only seconds of incubation with FTY720 at 37 degrees C and washing, and continues for days before recovery of surface expression and functions. The timing and extent of S1P-R internalization are highly dependent on FTY720 concentration. FTY720 is therefore an S1P-GPCR-selective and noncompetitive inhibitor with a unique mechanism of action.
Expression, Purification, and Characterization of gp160e, the Soluble, Trimeric Ectodomain of the Simian Immunodeficiency Virus Envelope Glycoprotein, gp160 (2000)

The envelope glycoprotein, gp160, of simian immunodeficiency virus (SIV) shares approximately 25% sequence identity with gp160 from the human immunodeficiency virus, type I, indicating a close structural similarity. As a result of binding to cell surface CD4 and co-receptor (e.g. CCR5 and CXCR4), both SIV and human immunodeficiency virus gp160 mediate viral entry by membrane fusion. We report here the characterization of gp160e, the soluble ectodomain of SIV gp160. The ectodomain has been expressed in both insect cells and Chinese hamster ovary (CHO)-Lec3.2.8.1 cells, deficient in enzymes necessary for synthesizing complex oligosaccharides. Both the primary and a secondary proteolytic cleavage sites between the gp120 and gp41 subunits of gp160 were mutated to prevent cleavage and shedding of gp120. The purified, soluble glycoprotein is shown to be trimeric by chemical cross-linking, gel filtration chromatography, and analytical ultracentrifugation. It forms soluble, tight complexes with soluble CD4 and a number of Fab fragments from neutralizing monoclonal antibodies. Soluble complexes were also produced of enzymatically deglycosylated gp160e and of gp160e variants with deletions in the variable segments.
SMPTE Tutorial Paper: Digital Component Television Made Simple (1985)

This tutorial article is intended to leave a vivid and memorable recollection of the essentials of digitization and the ramifications of the spatial loci of the samples taken. No stand is taken on any sampling method. Any arguments are those made previously by others, and are couched in the very simplest of analogs. The intent is to create an understanding where none exists, rather than expand upon an incomplete understanding.
Uptake of Leishmania major by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity (2006)

Uptake of Leishmania major by dendritic cells (DCs) results in activation and interleukin (IL)-12 release. Infected DCs efficiently stimulate CD4- and CD8- T cells and vaccinate against leishmaniasis. In contrast, complement receptor 3-dependent phagocytosis of L. major by macrophages (MPhi) leads exclusively to MHC class II-restricted antigen presentation to primed, but not naive, T cells, and no IL-12 production. Herein, we demonstrate that uptake of L. major by DCs required parasite-reactive immunoglobulin (Ig)G and involved FcgammaRI and FcgammaRIII. In vivo, DC infiltration of L. major-infected skin lesions coincided with the appearance of antibodies in sera. Skin of infected B cell-deficient mice and Fcgamma-/- mice contained fewer parasite-infected DCs in vivo. Infected B cell-deficient mice as well as Fcgamma-/- mice (all on the C57BL/6 background) showed similarly increased disease susceptibility as assessed by lesion volumes and parasite burdens. The B cell-deficient mice displayed impaired T cell priming and dramatically reduced IFN-gamma production, and these deficits were normalized by infection with IgG-opsonized parasites. These data demonstrate that DC and MPhi use different receptors to recognize and ingest L. major with different outcomes, and indicate that B cell-derived, parasite-reactive IgG and DC FcgammaRI and FcgammaRIII are essential for optimal development of protective immunity.
Hepatitis C Genotyping by Denaturing High-Performance Liquid Chromatography (2004)

Determination of the hepatitis C virus (HCV) genotype for infected patients increasingly has become accepted as the standard of care. Genotype assignment helps in assessing disease prognosis and assists in establishing the appropriate duration of treatment. The great genetic diversity of HCV, with 11 major genotypes and >70 subtypes, contributes to the technical difficulty of genotype testing. While the "gold standard" for testing is nucleic acid sequencing, a variety of hybridization assays, including the line probe assay, have been developed to provide more rapid and accessible forms of testing. The aim of this study was to determine whether denaturing high-performance liquid chromatography (dHPLC) could be used as a clinical method for distinguishing HCV genotypes 1, 2, 3, and 4. A portion of the 5' untranslated region of the HCV genome was amplified by heminested multiplex reverse transcription PCR. The two amplicons then were analyzed by dHPLC analysis and compared to the genotypes determined by sequence analysis. After 115 specimens were analyzed as standards, 200 masked specimens (specimens whose identity was not known before testing) were analyzed to determine the concordance of the assay. The assay had a concordance of 96% at the genotype level and a concordance of 87% at the subtype level. However, the dHPLC method was not as accurate as other reported methods of HCV genotyping. This is the first time that HCV genotyping has been performed by dHPLC.
Statistical post-editing of a rule-based machine translation system (2009)

Automatic post-editing (APE) systems aim at correcting the output of machine translation systems to produce better quality translations, i.e. produce translations can be manually post-edited with an increase in productivity. In this work, we present an APE system that uses statistical models to enhance a commercial rule-based machine translation (RBMT) system. In addition, a procedure for effortless human evaluation has been established. We have tested the APE system with two corpora of different complexity. For the Parliament corpus, we show that the APE system significantly complements and improves the RBMT system. Results for the Protocols corpus, although less conclusive, are promising as well. Finally, several possible sources of errors have been identified which will help develop future system enhancements.
From RGB-D Images to RGB Images (2015)

Mining object-level knowledge, that is, building a comprehensive category model base, from a large set of cluttered scenes presents a considerable challenge to the field of artificial intelligence. How to initiate model learning with the least human supervision (i.e., manual labeling) and how to encode the structural knowledge are two elements of this challenge, as they largely determine the scalability and applicability of any solution. In this article, we propose a model-learning method that starts from a single-labeled object for each category, and mines further model knowledge from a number of informally captured, cluttered scenes. However, in these scenes, target objects are relatively small and have large variations in texture, scale, and rotation. Thus, to reduce the model bias normally associated with less supervised learning methods, we use the robust 3D shape in RGB-D images to guide our model learning, then apply the properly trained category models to both object detection and recognition in more conventional RGB images. In addition to model training for their own categories, the knowledge extracted from the RGB-D images can also be transferred to guide model learning for a new category, in which only RGB images without depth information in the new category are provided for training. Preliminary testing shows that the proposed method performs as well as fully supervised learning methods.
Using Induced Microseismicity To Monitor Hydraulic Fracture Treatment: A Tool To Improve Completion Techniques and Reservoir Management (2006)

Abstract The organic-rich shale gas fields underlying the Appalachian, Illinois and Michigan basins are potentially the most productive source of natural gas in the northeast United States. Similarly to the Barnett Shale in Texas and the Fayetteville Shale in Arkansas, considerable volumes of gas are currently produced from these unconventional Devonian shale reservoirs using traditional and more modern well log evaluations techniques and completion methods. Among others, two main geologic factors govern the production from these gas-bearing formations: ultra low matrix porosity and permeability and fracture-induced permeability. Devonian Shales are extremely low porosity reservoirs that must be effectively hydraulically fracture stimulated. Additionally, analysis of these gas fields illustrates how structural geology (by the means of basement structure influence, differential shortening effect, etc.) yields stress field variations both laterally and with depth. To avoid making too many assumptions as to the induced fracture geometry and to better understand the created fracture geometry for various completion designs, monitoring of the induced microseismic activity may be used. Using a couple of examples from various formations (e.g., tight gas sand, shale gas, etc.), this paper highlights how microseismic monitoring of hydraulic fracture treatments can provide key information to characterize fracture development and geometry.
Ribozyme-mediated in vitro cleavage of transcripts arising from the major transforming genes of human papillomavirus type 16. (1994)

Human papillomaviruses (HPV) have been strongly implicated as important cofactors in the development of several human malignancies, particularly anogenital carcinomas. Products arising from the E6 and E7 open reading frames (ORFs) from HPV-16, a type commonly associated with human cervical carcinoma, are essential for viral transformation. Unfortunately, a highly effective treatment for this infection is not available. To develop a novel treatment for this disease, ribozymes were designed to cleave all transcripts encoding HPV-16 E6 and E7 ORFs in proximity to their translational start sites ("AUG"). Cleavage sites for Rz110 and Rz558 occur immediately 3' to nucleotides 110 and 558 of the viral genomic DNA, respectively. Oligonucleotides corresponding to these ribozymes were synthesized and inserted into a eucaryotic viral vector derived from the nonpathogenic parvovirus, adeno-associated virus. Ribozyme transcription from this vector, termed CWRT7:SVN, is under control of both the highly active Rous sarcoma virus long terminal repeat and bacteriophage T7 promoters. T7 transcripts of the E6 and E7 ribozymes efficiently cleaved their cognate targets in vitro under a variety of conditions, including physiological temperature. These results may provide the basis for the development of a ribozyme-based, gene therapeutic treatment for HPV-associated diseases.
Kochia – Poor Man's Alfalfa – Shows Potential as Feed (1980)

This material was digitized as part of a cooperative project between the Society for Range Management, the National Agricultural Library, and the University of Arizona Libraries.
Tensor Completion for Estimating Missing Values in Visual Data (2012)

In this paper, we propose an algorithm to estimate missing values in tensors of visual data. The values can be missing due to problems in the acquisition process or because the user manually identified unwanted outliers. Our algorithm works even with a small amount of samples and it can propagate structure to fill larger missing regions. Our methodology is built on recent studies about matrix completion using the matrix trace norm. The contribution of our paper is to extend the matrix case to the tensor case by proposing the first definition of the trace norm for tensors and then by building a working algorithm. First, we propose a definition for the tensor trace norm that generalizes the established definition of the matrix trace norm. Second, similarly to matrix completion, the tensor completion is formulated as a convex optimization problem. Unfortunately, the straightforward problem extension is significantly harder to solve than the matrix case because of the dependency among multiple constraints. To tackle this problem, we developed three algorithms: simple low rank tensor completion (SiLRTC), fast low rank tensor completion (FaLRTC), and high accuracy low rank tensor completion (HaLRTC). The SiLRTC algorithm is simple to implement and employs a relaxation technique to separate the dependent relationships and uses the block coordinate descent (BCD) method to achieve a globally optimal solution; the FaLRTC algorithm utilizes a smoothing scheme to transform the original nonsmooth problem into a smooth one and can be used to solve a general tensor trace norm minimization problem; the HaLRTC algorithm applies the alternating direction method of multipliers (ADMMs) to our problem. Our experiments show potential applications of our algorithms and the quantitative evaluation indicates that our methods are more accurate and robust than heuristic approaches. The efficiency comparison indicates that FaLTRC and HaLRTC are more efficient than SiLRTC and between FaLRTC an- HaLRTC the former is more efficient to obtain a low accuracy solution and the latter is preferred if a high-accuracy solution is desired.
Factors governing the nitration of cellulose. (1946)

This thesis document was issued under the authority of another institution, not NPS. At the time it was written, a copy was added to the NPS Library collection for reasons not now known. It has been included in the digital archive for its historical value to NPS. Not believed to be a CIVINS (Civilian Institutions) title.
The detection and initial characterization of colony-stimulating factors in synovial fluid. (1988)

In this study which included 16 patients with inflammatory or non-inflammatory arthropathies, human granulocyte-macrophage colony-stimulating activity was detected in synovial fluid. This was attributable to the presence of colony-stimulating factor(s) (CSF), as a direct action on human bone marrow progenitor cells was demonstrated using clone transfer experiments. Samples of synovial fluid also stimulated the growth of murine macrophage colonies and induced differentiation in the murine myelomonocytic leukemia cell line, WEHI-3B(D+), which are characteristic properties of human macrophage-CSF or granulocyte-CSF respectively. These findings and the results of preliminary fractionation procedures suggested that the colony-stimulating activity in synovial fluid was not explicable by the presence of any one of the well-characterized human CSF acting in isolation. This provides a new insight into the pathogenesis of inflammatory arthropathies and supports the hypothesis that CSF have important roles in vivo in addition to the regulation of haemopoiesis.
HDAC2 (Histone deacetylase 2): A critical factor in environmental enrichment‐mediated stroke recovery (2020)

Environmental enrichment (EE) is a generally accepted strategy to promote stroke recovery and its beneficial effect is positively correlated with neuroplasticity. However, the mechanisms underlying it remain elusive. Histone deacetylase 2 (HDAC2), a negative regulator of neuroplasticity, is up-regulated after stroke. Thus, we hypothesized that HDAC2 may participate in EE-mediated stroke recovery. In this study, focal stroke was induced by photothrombosis in male mice exposing to EE or standard housing (SH) conditions. Recombinant virus vectors, including Ad-HDAC2-Flag, AAV-CAG-EGFP-Cre, LV-shHDAC2, or their controls were microinjected into the motor cortex at 3 days before stroke. Grid-walking and cylinder tasks were conducted to assess motor function. Western blot and immunostaining were used to uncover the mechanisms underlying EE-mediated stroke recovery. We found that EE exposure reversed stroke-induced HDAC2 up-regulation, implicating HDAC2 in EE-mediated functional recovery. Importantly, EE-dependent stroke recovery was counteracted by over-expressing HDAC2, and HDAC2 knockdown promoted functional recovery from stroke to the similar extent as EE exposure. Moreover, the knockdown of HDAC2 epigenetically enhanced expressions of neurotrophins and neuroplasticity-related proteins, with similar effects as EE, and consequently, whole brain and corticospinal tract (CST) rewiring. Together, our findings indicate that HDAC2 is critical for EE-dependent functional restoration. Precisely targeting HDAC2 may mimic EE and serve as a novel therapeutic strategy for stroke recovery.
Temporal memory deficits in Alzheimer's mouse models: rescue by genetic deletion of BACE1 (2006)

Transgenic mouse models of Alzheimer's disease (AD) exhibit amyloid-beta (Abeta) accumulation and related cognitive impairments. Although deficits in hippocampus-dependent place learning have been well characterized in Alzheimer's transgenic mice, little is known about temporal memory function in these AD models. Here, we applied trace fear conditioning to two different Alzheimer's mouse models and investigated the relationship between pathogenic Abeta and temporal memory deficits. This behavioral test requires hippocampus-dependent temporal memory processing as the conditioned and unconditioned stimuli are separated by a trace interval of 30 s. We found that both amyloid precursor protein (APP) transgenic (Tg2576) and APP/presenilin (PS)1 transgenic (Tg6799) mice were impaired in memorizing this association across the time gap. Both transgenic groups performed as well as wild-type control mice in delay fear conditioning when the trace interval was removed, indicating that the trace conditioning deficits are hippocampus-specific. Importantly, Tg6799 mice engineered to lack the major Alzheimer's beta-secretase (beta-site APP-cleaving enzyme 1: BACE1) showed behavioral rescue from temporal memory deficits. Elevated levels of soluble Abeta oligomers found in Tg6799+ mouse brains returned to wild-type control levels without changes in APP/PS1 transgene expression in BACE1-/- * Tg6799+ bigenic mouse brains, suggesting Abeta oligomers as potential mediators of memory loss. Thus, trace fear conditioning is a useful assay to test the mechanisms and therapeutic interventions for Abeta-dependent deficits in temporal associative memory. Our gene-based approach suggests that lowering soluble Abeta oligomers by inhibiting BACE1 may be beneficial for alleviating cognitive disorders in AD.
Effect of decoyinine on the regulation of alpha-amylase synthesis in Bacillus subtilis (1987)

Decoyinine, an inhibitor of GMP synthetase, allows sporulation in Bacillus subtilis to initiate and proceed under otherwise catabolite-repressing conditions. The effect of decoyinine on alpha-amylase synthesis in B. subtilis, an event which exhibits regulatory features resembling sporulation initiation, was examined. Decoyinine did not overcome catabolite repression of alpha-amylase synthesis in a wild-type strain of B. subtilis but did cause premature and enhanced synthesis in a mutant strain specifically blocked in catabolite repression of alpha-amylase synthesis. Decoyinine had no effect on alpha-amylase enzymatic activity. Thus, it appears that the catabolite control mechanisms governing alpha-amylase synthesis and sporulation in B. subtilis differ in their responses to decoyinine and hence must consist at least partially of separate components.
Novel chemotherapeutic agents in clinical development (1991)

The development of new chemotherapeutic agents for cancer treatment is pursued with the hope of finding compounds with novel chemical characteristics, unique mechanisms of action, and with improved therapeutic indexes. Seven novel agents at different stages of clinical development have been selected for review. D1694 is a thymidylate synthase inhibitor that has intriguing preclinical activity. The anthrapyrazoles consist of three analogues that are undergoing phase II testing at present. One of these agents, CI-941, has been reported to have significant clinical activity in breast cancer. Lometrexol is an inhibitor of glycinamide ribonuclide transformylase, a critical enzyme in purine biosynthesis, that is undergoing phase II testing. Taxotere, a semisynthetic analogue of taxol that stabilizes microtubules, is currently undergoing phase I testing. Gemcitabine, a fluorinated analogue of deoxycytidine that can inhibit ribonucleotide reductase and be incorporated into DNA, is undergoing phase II testing. BMY-25067 is a mitomycin C analogue that is less myelosuppressive and more active than mitomycin C in preclinical models. Topotecan, a topoisomerase I inhibitor, has been shown to cause myelosuppression as the dose-limiting toxicity in phase I testing. Although each of these agents have some unique and novel characteristics that merit their clinical testing, these agents' long-range clinical role will depend on their efficacy in randomized phase III comparative trials.
Dissecting complex transcriptional responses using pathway-level scores based on prior information (2007)

By avoiding the thresholding of individual genes, pathway-level analysis of differential expression based on prior information can be considerably more sensitive to subtle changes in gene expression than gene-level analysis. The methods are technically straightforward and yield results that are easily interpretable, both biologically and statistically.
Nanopore basecalling from a perspective of instance segmentation (2020)

Our results show that formulating the basecalling problem as a one-dimensional segmentation task is a promising approach, which does basecalling and segmentation jointly.