gebhart/patrepeval huggingface dataset:
Targeted DNA Methylation Using an Artificially Bisected M.HhaI Fused to Zinc Fingers (2012)

Little is known about the effects of single DNA methylation events on gene transcription. The ability to direct the methylation toward a single unique site within a genome would have broad use as a tool to study the effects of specific epigenetic changes on transcription. A targeted enzyme might also be useful in a therapy for diseases with an epigenetic component or as a means to site-specifically label DNA. Previous studies have sought to target methyltransferase activity by fusing DNA binding proteins to methyltransferases. However, the methyltransferase domain remains active even when the DNA binding protein is unbound, resulting in significant off-target methylation. A better strategy would make methyltransferase activity contingent upon the DNA binding protein's association with its DNA binding site. We have designed targeted methyltransferases by fusing zinc fingers to the fragments of artificially-bisected, assembly-compromised methyltransferases. The zinc fingers' binding sites flank the desired target site for methylation. Zinc finger binding localizes the two fragments near each other encouraging their assembly only over the desired site. Through a combination of molecular modeling and experimental optimization in E. coli, we created an engineered methyltransferase derived from M.HhaI with 50-60% methylation at a target site and nearly undetectable levels of methylation at a non-target M.HhaI site (1.4 ± 2.4%). Using a restriction digestion assay, we demonstrate that localization of both fragments synergistically increases methylation at the target site, illustrating the promise of our approach.
TARGETING THE IL-15 RECEPTOR WITH AN ANTAGONIST IL-15/Fcγ2a PROTEIN BLOCKS DTH AND ENHANCES THE ACCEPTANCE OF ISLET ALLOGRAFTS (1998)

713 Owing to shared receptor components, the biological activities of IL-15 are similar to those of IL-2. However the patterns of tissue expression of IL-2/IL-2Rα and IL-15/IL-15Rα differ. The development of agents targeting the receptor and signaling elements of IL-15 may provide a new perspective for treatment of diseases associated with expression of IL-15/IL-15R. We designed, genetically constructed and expressed a receptor site specific IL-15 antagonist by mutating glutamine residues within the C-terminus of IL-15 to aspartic acid and linked this mutant IL-15 to murine Fcγ2a. These IL-15 mutant/Fcγ2a proteins specifically bound to the IL-15R, competitively inhibited IL-15 triggered cell proliferation and did not activate the Jak-STAT signaling pathway. We examined the immunosuppressive activity of this agent because of prolonged half-life and the potential for destruction of IL-15R+ leukocytes. The IL-15 mutant/Fcγ2a proteins markedly attenuated antigen specific DTH responses in Balb-c mice comparing with the responses in the mice treated with control IgG. Intraperitoneal injection of this mutant protein enhanced the acceptance of crude islet allografts from DBA/2J(H-2d) to B6AF1(H-2b/d,k) rendered diabetic by injection of streptozotocin (15 vs>65 days; control IgG vs IL-15 mutant/Fcγ2a treatment, mean survival time, 8 mice in each group). Quantitative RT-PCR analysis of the grafts and lymph nodes also revealed decreased expression of immune activation genes following IL-15 mutant/Fcγ2a administration. Conclusion: These findings suggest that i) IL-15/IL-15R+ cells are crucial to these T-cell dependent immune responses, and ii) treatment with IL-15 mutant/Fcγ2a fusion protein may ameliorate T-cell dependent immune/inflammatory diseases.
New Insights into the Mechanisms of Protein Palmitoylation (2003)

Since its discovery more than 30 years ago, protein palmitoylation has been shown to have a role in protein-membrane interactions, protein trafficking, and enzyme activity. Until recently, however, the molecular machinery that carries out reversible palmitoylation of proteins has been elusive. In fact, both enzymatic and nonenzymatic S-acylation reaction mechanisms have been proposed. Recent reports of protein palmitoyltransferases in Saccharomyces cerevisiae and Drosophila provide the first glimpse of enzymes that carry out protein palmitoylation. Equally important is the mechanism of depalmitoylation. Two major classes of protein palmitoylthioesterases have been described. One family is lysosomal and is involved in protein degradation. The second is cytosolic and removes palmitoyl moieties preferentially from proteins associated with membranes. This review discusses recent advances in the understanding of mechanisms of addition of palmitate to proteins and removal of palmitate from proteins.
Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry (1997)

Entry of human immunodeficiency virus type 1 (HIV-1) requires CD4 and one of a family of related seven-transmembrane-domain coreceptors. Macrophage-tropic HIV-1 isolates are generally specific for CCR5, a receptor for the CC chemokines RANTES, MIP-1alpha, and MIP-1beta, while T-cell line-tropic viruses tend to use CXCR4 (also known as fusin, LESTR, or HUMSTR). Like HIV-1, simian immunodeficiency virus (SIV) requires CD4 on the target cell surface; however, whether it also requires a coreceptor is not known. We report here that several genetically divergent SIV isolates, including SIVmac, SIVsmSL92a, SIVsmLib-1, and SIVcpzGAB, can use human and rhesus CCR5 for entry. CXCR4 did not facilitate entry of any of the simian viruses tested, nor did any of the other known chemokine receptors. Moreover, SIVmac251 that had been extensively passaged in a human transformed T-cell line retained its use of CCR5. Rhesus and human CCR5 differed at only eight amino acid residues, four of which were in regions of the receptor that could be exposed, two in the amino-terminal extracellular region and two in the second extracellular loop. The human coreceptor was as active as the simian for SIV entry. In addition, HIV-1 was able to use the rhesus homologs of the human coreceptors, CCR5 and CXCR4. The SIV strains tested were specific for CCR5 regardless of whether they were able to replicate in transformed T-cell lines or macrophages and whether they were phenotypically syncytium inducing or noninducing in MT-2 cells. However, SIV replication was not restricted to cells expressing CCR5. SIV strains replicated efficiently in the human transformed lymphoid cell line CEMx174, which does not express detectable amounts of transcripts of CCR5. SIV also replicated in human peripheral blood mononuclear cells that were genetically deficient in CCR5. These findings indicated that, in addition to CCR5, SIV can use one or more unknown coreceptors that are expressed on human PBMCs and CEMx174 cells.
Improvement of Adjuvant Systems to Obtain a Cost-Effective Production of High Levels of Specific IgY (2007)

Incomplete Freund's adjuvant (IFA) is used as standard adjuvant for the production of specific antibodies. In this study, we evaluated the ability of supplementation of IFA with 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] or C-phosphate-guanosine-oligodeoxynucleotide (CpG-ODN) to enhance the quantity of specific IgY found in the eggs of hyperimmunized laying hens. In this comparative study, the fimbrial adhesin F4 of porcine enterotoxigenic Escherichia coli was used as prototype immunogen. Hens of 3 groups received by i.m. injection 20 microg of purified F4 adhesin emulsified with 1 of the following adjuvants: 0.5 mL of IFA alone (F4-IFA group), 0.5 mL of IFA supplemented with 285.6 ng of 1alpha,25(OH)(2)D(3) (F4-IFA-D(3) group), or 0.5 mL of IFA supplemented with 10 microg of CpG-ODN (F4-IFA-CpG group). Hens of 2 control groups received PBS or purified F4 alone. Immunization was repeated after 2 and 5 or 7 wk. Eggs were collected at 3- to 4-d intervals from preimmunization to d 79, and whole eggs were tested to measure the quantity of anti-F4 IgY by a standardized indirect ELISA. The quantity of specific anti-F4 IgY present in eggs from immunized hens of the F4-IFA group increased from d 13 to 79, corresponding to the end of the experiment. The values for this group at each time were considered as 100%. Results obtained for the other adjuvants were expressed in relation to this reference method. Supplementation of IFA with 1alpha,25(OH)(2)D(3) did not result in any enhancement of the quantity of anti-F4 IgY present in the eggs. On the other hand, supplementation of IFA with CpG-ODN resulted in an enhancement of yield up to 942% of the F4-specific antibody response. Moreover, the use of CpG-ODN is a cost-effective and ethical refinement for the production of specific antibodies, permitting a reduction in the number of immunizations needed. In conclusion, this study provides strong evidence for the use of IFA supplemented with CpG-ODN rather than IFA alone for the production of high levels of specific antibody in laying hens.
ECONOMIC DESIGN OF REFRIGERATED AUTOMATED STORAGE AND RETRIEVAL SYSTEMS (1999)

The objective of this paper is the development of a design model for refrigerated automated storage and retrieval systems (R-AS/RS). Compared with ordinary unit-load AS/RS, the R-AS/RS under this study has several different design and operating characteristics: (I) greater emphasis is placed on the storage function and so it has a double-depth lane in the storage rack; (2) cooling units are required to maintain a cold temperature environment in the system; (3) the maximum number of storage orders handled per unit time is limited by the system capacity. Considering the above characteristics, the design problem is formulated as a non-linear mixed integer programming problem in which the cost of the system is minimized. The decision variables are the storage volume, the number of storage and retrieval (S/R) machines, the type and number of cooling units, and the physical configuration of the building. A case problem is solved to illustrate the model.
Mode Dependent Coding Tools for Video Coding (2013)

This paper provides an overview of the mode dependent coding tools in the development of video coding technology. In video coding, the prediction mode is closely related with the local image statistical characteristics. For instance, the angular intra mode contains the oriented structure information and the interpartition mode can reveal the local texture properties. Characterized by this fact, the prediction mode can be employed to facilitate the further encoding process, such as transform and coefficient coding. Recently, many mode dependent coding tools were proposed to provide more flexibility and thereby improve the compression performance. In general, these coding tools can be classified into three categories: mode dependent transform, residual reorder before transformation and coefficient scan after transformation. In this paper, these advanced coding algorithms are detailed and experiments are conducted to demonstrate their superior compression performance.
A recurrent encoder-decoder approach with skip-filtering connections for monaural singing voice separation (2017)

The objective of deep learning methods based on encoder-decoder architectures for music source separation is to approximate either ideal time-frequency masks or spectral representations of the target music source(s). The spectral representations are then used to derive time-frequency masks. In this work we introduce a method to directly learn time-frequency masks from an observed mixture magnitude spectrum. We employ recurrent neural networks and train them using prior knowledge only for the magnitude spectrum of the target source. To assess the performance of the proposed method, we focus on the task of singing voice separation. The results from an objective evaluation show that our proposed method provides comparable results to deep learning based methods which operate over complicated signal representations. Compared to previous methods that approximate time-frequency masks, our method has increased performance of signal to distortion ratio by an average of 3.8 dB.
The relationship between stress fiber-like structures and nascent myofibrils in cultured cardiac myocytes. (1984)

The topographical relationship between stress fiber-like structures (SFLS) and nascent myofibrils was examined in cultured chick cardiac myocytes by immunofluorescence microscopy. Antibodies against muscle-specific light meromyosin (anti-LMM) and desmin were used to distinguish cardiac myocytes from fibroblastic cells. By various combinations of staining with rhodamine-labeled phalloidin, anti-LMM, and antibodies against chick brain myosin and smooth muscle alpha-actinin, we observed the following relationships between transitory SFLS and nascent and mature myofibrils: (a) more SFLS were present in immature than mature myocytes; (b) in immature myocytes a single fluorescent fiber would stain as a SFLS distally and as a striated myofibril proximally, towards the center of the cell; (c) in regions of a myocyte not yet penetrated by the elongating myofibrils, SFLS were abundant; and (d) in regions of a myocyte with numerous mature myofibrils, SFLS had totally disappeared. Spontaneously contracting striated myofibrils with definitive Z-band regions were present long before anti-desmin localized in the I-Z-band region and long before morphologically recognizable structures periodically link Z-bands to the sarcolemma. These results suggest a transient one-on-one relationship between individual SFLS and newly emerging individual nascent myofibrils. Based on these and other relevant data, a complex, multistage molecular model is presented for myofibrillar assembly and maturation. Lastly, it is of considerable theoretical interest to note that mature cardiac myocytes, like mature skeletal myotubes, lack readily detectable stress fibers.
Trichuris suis therapy in Crohn’s disease (2004)

Background: Crohn’s disease is common in highly industrialised Western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Thus exposure to helminths may help prevent or even ameliorate Crohn’s disease. Aims: The aim of the study was to determine the safety and possible efficacy of the intestinal helminth Trichuris suis in the treatment of patients with active Crohn’s disease. Patients: Twenty nine patients with active Crohn’s disease, defined by a Crohn’s disease activity index (CDAI) ⩾220 were enrolled in this open label study. Methods: All patients ingested 2500 live T suis ova every three weeks for 24 weeks, and disease activity was monitored by CDAI. Remission was defined as a decrease in CDAI to less than 150 while a response was defined as a decrease in CDAI of greater than 100. Results: At week 24, 23 patients (79.3%) responded (decrease in CDAI &gt;100 points or CDAI &lt;150) and 21/29 (72.4%) remitted (CDAI &lt;150). Mean CDAI of responders decreased 177.1 points below baseline. Analysis at week 12 yielded similar results. There were no adverse events. Conclusions: This new therapy may offer a unique, safe, and efficacious alternative for Crohn’s disease management. These findings also support the premise that natural exposure to helminths such as T suis affords protection from immunological diseases like Crohn’s disease.
Leukocyte Coping Capacity: A Novel Technique for Measuring the Stress Response in Vertebrates (2003)

Methods used to quantify the stress response in animals are vital tools in many areas of biology. Here we describe a new method of measuring the stress response, which provides rapid results and can be used in the field or laboratory. After a stressful event, we measure the capacity of circulating leukocytes to produce a respiratory burst in vitro in response to challenge by phorbol myristate acetate (PMA). During the respiratory burst leukocytes produce oxygen free radicals, and the level of production can be measured directly as chemiluminescence. When in vitro PMA-stimulated whole blood chemiluminescence is measured directly after a stressful event, we define the response as the leukocyte coping capacity (LCC). In an experiment badgers (Meles meles), which were caught as part of an on-going population study, were either transported to a central site prior to blood sampling or blood was collected at their site of capture. Transported animals had a significantly lower LCC and showed changes in leukocyte composition that were indicative of stress. We conclude that the stress of transport reduced LCC in badgers and that LCC serves as a quantitative measure of stress. Potential applications of this method are discussed.
A systematic review of risk factors for cerebral palsy in children born at term in developed countries (2012)

Ten consistent risk factors have been identified, some with potential for prevention. Efforts to prevent these risk factors to interrupt the pathway to CP should be extended.
A randomized trial of peak‐flow and symptom‐based action plans in adults with moderate‐to‐severe asthma (2001)

Use of written action plans, combined with regular contact to reinforce self-management, improved airway reactivity and reduced health care utilization. However, use of PFM was not superior to symptom-based plans.
Identification of a signal in a murine retrovirus that is sufficient for packaging of nonretroviral RNA into virions (1988)

A region near the 5' end of Moloney murine leukemia virus (MoMLV) is required for packaging of viral RNA into virions. Retroviral vectors based on MoMLV have been constructed that are also efficiently packaged into virions despite removal of most of the interior region of the parental virus. To further localize sequences which are sufficient for packaging, we inserted various fragments from an MoMLV-based retroviral vector into a nonretroviral transcription unit, transfected these constructs into retrovirus-packaging cells, and measured packaging of RNA transcribed from these constructs into virions. Transcripts from some of these constructs were packaged at least as well as those from the parental vector or MoMLV itself. Sequences extending into the gag region, but not the long terminal repeat or tRNA-binding sequences, were required for efficient RNA packaging. RNAs transcribed from constructs which did not contain an insert, or in which the orientation of the insert was reversed, were not packaged at detectable levels. These studies define sequences which are necessary and sufficient for encapsidation of murine leukemia virus RNA into virions.
Topic Cube: Topic Modeling for OLAP on Multidimensional Text Databases (2009)

As the amount of textual information grows explosively in various kinds of business systems, it becomes more and more desirable to analyze both structured data records and unstructured text data simultaneously. While online analytical processing (OLAP) techniques have been proven very useful for analyzing and mining structured data, they face challenges in handling text data. On the other hand, probabilistic topic models are among the most effective approaches to latent topic analysis and mining on text data. In this paper, we propose a new data model called topic cube to combine OLAP with probabilistic topic modeling and enable OLAP on the dimension of text data in a multidimensional text database. Topic cube extends the traditional data cube to cope with a topic hierarchy and store probabilistic content measures of text documents learned through a probabilistic topic model. To materialize topic cubes efficiently, we propose a heuristic method to speed up the iterative EM algorithm for estimating topic models by leveraging the models learned on component data cells to choose a good starting point for iteration. Experiment results show that this heuristic method is much faster than the baseline method of computing each topic cube from scratch. We also discuss potential uses of topic cube and show sample experimental results.
Studies on delayed systemic effects of ultraviolet B radiation on the induction of contact hypersensitivity, 3. Dendritic cells from secondary lymphoid organs are deficient in interleukin‐12 production and capacity to promote activation and differentiation of T helper type 1 cells (2000)

Ultraviolet-B radiation (UVR) of mouse skin promotes both local and systemic immune aberrations that are thought to be important in the pathogenesis of cutaneous malignancies. Acute, low-dose UVR regimens inhibit the induction of contact hypersensitivity (CH) in genetically susceptible mice by TNF-alpha-dependent mechanisms. In addition, these regimens also promote the development of tolerance when hapten is applied to the UVR-exposed site at the completion of the radiation treatment protocol. A third immune abnormality is also observed in mice exposed to acute, low-dose UVR. This abnormality, which develops within 48-72 hr of the completion of the UVR regimen, has been described among antigen-presenting cells within secondary lymphoid organs, including lymph nodes that do not drain the site of irradiation. Dendritic cells (DCs) from lymph nodes and spleens of mice exposed to UVR lack the capacity to induce CH if they are derivatized with hapten and injected intracutaneously into naive mice. The DC defect is related to the production of and systemic dissemination of interleukin-10 (IL-10) by keratinocytes within the epidermis of the UVR-exposed skin. We have now examined the nature of the functional aberration that exists among DCs within the secondary lymphoid organs of UVR-exposed mice by examining the capacity of DCs to express co-stimulatory molecules, and their ability to activate ovalbumin (OVA) -specific DO11.10 T-cell receptor transgenic T cells in vitro. Our results indicate that DCs from UVR-exposed mice produced insufficient amounts of IL-12. When pulsed with OVA, these cells were capable of inducing proliferation among DO11.10 T cells in vitro, but the responding cells produced neither IFN-gamma nor IL-10 and IL-4. A similar antigen-presenting cell defect was generated in mice treated with a subcutaneous injection of IL-10. We conclude that acute, low-dose UVR creates an IL-10-dependent functional deficit in DCs in secondary lymphoid organs, and that this defect robs UVR-exposed mice of the capacity to develop CH when hapten is painted epicutaneously.
Isolation of Total RNA from Bacteria (1998)

The susceptibihty of RNA to degradation by exogenous and endogenous RNase activity following cell lysis has been well documented (,). Moreover RNA usually occurs complexed with protein from which it must be released. Precautions to be taken against exogenous RNase include the use of plastic gloves, autoclavmg solutions after adding 0.1% (v/v) diethyl pyrocarbonate (DEPC; except Trrs, which reacts), and baking glassware, spatulas, and so forth at 180°C overnight ().