gebhart/patrepeval huggingface dataset:
Review on porcine endogenous retrovirus detection assays—impact on quality and safety of xenotransplants (2015)

Xenotransplantation of porcine organs, tissues, and cells inherits a risk for xenozoonotic infections. Viable tissues and cells intended for transplantation have to be considered as potentially contaminated non-sterile products. The demands on microbial testing, based on the regulatory requirements, are often challenging due to a restricted shelf life or the complexity of the product itself. In Europe, the regulatory framework for xenogeneic cell therapy is based on the advanced therapy medicinal products (ATMP) regulation (2007), the EMA CHMP Guideline on xenogeneic cell-based medicinal products (2009), as well as the WHO and Council of Europe recommendations. In the USA, FDA guidance for industry (2003) regulates the use of xenotransplants. To comply with the regulations, validated test methods need to be established that reveal the microbial status of a transplant within its given shelf life, complemented by strictly defined action alert limits and supported by breeding in specific pathogen-free (SPF) facilities. In this review, we focus on assays for the detection of the porcine endogenous retroviruses PERV-A/-B/-C, which exhibit highly polymorphic proviral loci in pig genomes. PERVs are transmitted vertically and cannot be completely eliminated by breeding or gene knock out technology. PERVs entail a public health concern that will persist even if no evidence of PERV infection of xenotransplant recipients in vivo has been revealed yet. Nevertheless, infectious risks must be minimized by full assessment of pigs as donors by combining different molecular screening assays for sensitive and specific detection as well as a functional analysis of the infectivity of PERV including an adequate monitoring of recipients.
Page allocation to reduce access time of physical caches (1990)

A simple modification to an operating system''s page allocation algorithm can give physically addressed caches the speed of virtually addressed caches. Colored page allocation reduces the number of bits that need to be translated before cache access, allowing large low-associativity caches to be indexed before address translation, which reduces the latency to the processor. The colored allocation also has other benefits: caches miss less (in general) and more uniformly, and the inclusion principle holds for second level caches with less associativity. However, the colored allocation requires main memory partitioning, and more common bits for shared virtual addresses. Simulation results show high non-uniformity of cache miss rates for normal allocation. Analysis demonstrates the extent of second-level cache inclusion, and the reduction in effective main-memory due to partitioning.
Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. (1998)

We have synthesized more than 80 novel triterpenoids, all derivatives of oleanolic and ursolic acid, as potential anti-inflammatory and chemopreventive agents. These triterpenoids have been tested for their ability to suppress the de novo formation of two enzymes, inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2), using IFN-gamma-stimulated primary mouse macrophages or lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as assay systems. Two synthetic oleananes, 3,12-dioxoolean-1-en-28-oic acid (TP-69) and 3,11-dioxoolean-1,12-dien-28-oic acid (TP-72), were highly active inhibitors of de novo formation of both iNOS and COX-2. Both TP-69 and TP-72 blocked the increase in iNOS or COX-2 mRNA induced by IFN-gamma or LPS. In addition, TP-72 suppressed NF-KB activation in primary macrophages treated with the combination of IFN-gamma and LPS or IFN-gamma and tumor necrosis factor. The 3-alpha(axial)-epimer of ursolic acid suppressed de novo formation of COX-2, in contrast to naturally occurring 3-beta(equatorial)-ursolic acid. Inhibitory effects of TP-69 or TP-72 on iNOS formation were not blocked by the glucocorticoid receptor antagonist RU-486, indicating that these triterpenoids do not act through the glucocorticoid receptor, nor does TP-72 act as an iNOS or COX-2 enzyme inhibitor when added to RAW cells in which synthesis of these two enzymes in response to LPS has already been induced. It may be possible to develop triterpenoids as useful agents for chemoprevention of cancer or other chronic diseases with an inflammatory component.
Supersaturation mechanism of drugs from solid dispersions with enteric coating agents. (1988)

The crystallization behavior of drugs from supersaturated solutions containing carboxymethylethylcellulose (CMEC) was investigated to clarify the mechanism of supersaturation phenomena from solid dispersions with enteric coating agents in JP XI 2nd fluid (pH 6.8). Nifedipine, griseofulvin and spironolactone were used as drugs. The rate of crystallization of all drugs was remarkably inhibited by the presence of CMEC.It was found that the inhibition was not due to solubilization of the drugs by CMEC.The crystallization kinetics from supersaturated solutions suggested that the process of crystal growth itself was directly inhibited. Physical properties of the crystallized mass were also investigated in the case of nifedipine. It was thought that the inhibitory effect of CMEC on the drug crystallization was due to the adsorption of CM EC at the solid-water interface at the stage in which a hydrophobic drug crystal surface was formed, and further drug molecules could not deposit easily on the crystal surface for the following reasons;(1) formation of a step or kink, which is necessary for the crystal growth, was inhibited by polymer adsorption, and (2) molecular diffusion to the crystal surface was inhibited by the adsorbed polymer.
Htra2-β 1 stimulates an exonic splicing enhancer and can restore full-length SMN expression to survival motor neuron 2 ( SMN2 ) (2000)

Spinal muscular atrophy (SMA), a common motor neuron disease in humans, results from loss of functional survival motor neuron (SMN1) alleles. A nearly identical copy of the gene, SMN2, fails to provide protection from SMA because of a single translationally silent nucleotide difference in exon 7. This likely disrupts an exonic splicing enhancer and causes exon 7 skipping, leading to abundant production of a shorter isoform, SMN2Delta7. The truncated transcript encodes a less stable protein with reduced self-oligomerization activity that fails to compensate for the loss of SMN1. This report describes the identification of an in vivo regulator of SMN mRNA processing. Htra2-beta1, an SR-like splicing factor and ortholog of Drosophila melanogaster transformer-2, promoted the inclusion of SMN exon 7, which would stimulate full-length SMN2 expression. Htra2-beta1 specifically functioned through and bound an AG-rich exonic splicing enhancer in SMN exon 7. This effect is not species-specific as expression of Htra2-beta1 in human or mouse cells carrying an SMN2 minigene dramatically increased production of full-length SMN2. This demonstrates that SMN2 mRNA processing can be modulated in vivo. Because all SMA patients retain at least one SMN2 copy, these results show that an in vivo modulation of SMN RNA processing could serve as a therapeutic strategy to prevent SMA.
New Boron Analogues of Pyrophosphates and Deoxynucleoside Boranophosphates (2001)

Tetraethyldicyanoborane pyrophosphate ( 2 ) and 3′‐(diethylphosphite‐cyanoborano)‐5′‐dimethoxytrityl.N 4 ‐benzoyl‐deoxycytidine ( 3 ) have been synthesized in 70% and 76% yields, respectively. The compatibility of the substituted boranophosphates with common protecting groups is hereby demonstrated. Boron containing biologically active compounds, such as nucleosides and nucleotides 1-6 and amino acids 7-9 are important due to their potential therapeutic activity, research and diagnostic applications. Many boron containing compounds have shown promising activity as anticancer, 1, 11, 12 antiinflammatory, 13 and antiosteoporotic 13 agents. Oligonucleotdes in which a non‐bridging oxygen atom is replaced by a borane(BH 3 ) group are a very important class of modified nucleic acids. 1, 3, 14-16 The BH 3 group is isoelectronic with oxygen in natural oligonucleotides and isoelectronic and isostructural with the oligonucleotide methyl phosphonates, which are nuclease resistant. On the other hand, the α‐borano triphosphates are good substrates for DNA polymerases and incorporation of boranophosphates into DNA causes an increase in the resistance to exo‐ and endonucleases 2, 17a as compared to non‐modified DNA. There are also notable applications of the α‐borano triphosphates in PCR sequencing 17a and nucleic acid detection 17b .
<title>Hierarchical block-matching algorithm using partial distortion criterion</title> (1998)

A new block matching algorithm (BMA) especially appropriate for large search areas is proposed. Motion vectors of causally adjacent blocks can be credible motion vector candidates in continuous motion fields. However, they are not helpful for searching complex or random motions. In order to remedy this problem, we propose a new two-step hierarchical block matching algorithm using spatial correlation in a motion field. In the first step, the candidates for an initial estimate consists of four motion vectors of adjacent blocks for searching continuous motion, and regularly sub-sampled points for searching complex or random motions. In the second step, the estimate is refined within a smaller search area by using full search BMA (FS- BMA). The straightforward application of the first step, however, tends to break data flow regularity due to random locations of four adjacent motion vectors. Therefore, in order to maintain consistent data flow in examining the four adjacent vectors, we introduce partial mean absolute difference which is calculated by suing a partial searching block rather than the whole block. Simulation result show that, in comparison with FS-BMA, the proposed algorithm reduces the computational complexity to 5.9 percent with negligible PSNR degradations. Furthermore, due to its regular data-flow, our scheme is especially suitable for hardware implementation.
Melanocyte lineage-specific antigens recognized by monoclonal antibodies NKI-beteb, HMB-50, and HMB-45 are encoded by a single cDNA. (1993)

The glycoproteins recognized by monoclonal antibody (MAb) NKI-beteb are among the best diagnostic markers for human melanoma. MAb NKI-beteb reacts with melanoma cells throughout tumor development and does not cross-react with other tumor or normal cells, except for cells of the melanocytic lineage. Two other melanocyte lineage-specific MAbs, HMB-50 and HMB-45, show a specificity and staining pattern strikingly similar to the ones observed for NKI-beteb. Herein, we demonstrate that all three MAbs recognize protein products encoded by a single cDNA. Expression of this cDNA in BLM cells results in immunoreactivity with all three MAbs. In addition, we demonstrate co-distribution of the RNA species detected by the cDNA with the proteins recognized by the MAbs in tissue sections.
Characterization and imaging in optically scattering media by use of laser speckle and a variable-coherence source (2000)

We demonstrate the application of laser-speckle statistics formed by a variable-coherence source illuminating a scattering medium, for determining the scattering parameter mu;(s)>(?) of a diffusion model for the medium. Furthermore, we apply this technique to visualize laterally localized inhomogeneities embedded within a highly scattering sample.
IL-21 Has a Pathogenic Role in a Lupus-Prone Mouse Model and Its Blockade with IL-21R.Fc Reduces Disease Progression (2007)

Systemic lupus erythematosus is a complex autoimmune disease characterized by dysregulated interactions between autoreactive T and B lymphocytes and the development of anti-nuclear Abs. The recently described pleiotropic cytokine IL-21 has been shown to regulate B cell differentiation and function. IL-21 is produced by activated T lymphocytes and its interactions with IL-21R are required for isotype switching and differentiation of B cells into Ab-secreting cells. In this report, we studied the impact of blocking IL-21 on disease in the lupus-prone MRL-Fas(lpr) mouse model. Mice treated for 10 wk with IL-21R.Fc fusion protein had reduced proteinuria, fewer IgG glomerular deposits, no glomerular basement membrane thickening, reduced levels of circulating dsDNA autoantibodies and total sera IgG1 and IgG2a, and reduced skin lesions and lymphadenopathy, compared with control mice. Also, treatment with IL-21R.Fc resulted in a reduced number of splenic T lymphocytes and altered splenic B lymphocyte ex vivo function. Our data show for the first time that IL-21 has a pathogenic role in the MRL-Fas(lpr) lupus model by impacting B cell function and regulating the production of pathogenic autoantibodies. From a clinical standpoint, these results suggest that blocking IL-21 in systemic lupus erythematosus patients may represent a promising novel therapeutic approach.
Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015 (2017)

Bill & Melinda Gates Foundation and Health Effects Institute.
Triggering RNAi with multifunctional RNA nanoparticles and their delivery (2015)

Proteins are considered to be the key players in structure, function, and metabolic regulation of our bodies. The mechanisms used in conventional therapies often rely on inhibition of proteins with small molecules, but another promising method to treat disease is by targeting the corresponding mRNAs. In 1998, Craig Mellow and Andrew Fire discovered dsRNA-mediated gene silencing <i>via</i> RNA interference or RNAi. This discovery introduced almost unlimited possibilities for new gene silencing methods, thus opening new doors to clinical medicine. RNAi is a biological process that inhibits gene expression by targeting the mRNA. RNAi-based therapeutics have several potential advantages (i) <i>a priori</i> ability to target any gene, (ii) relatively simple design process, (iii) site-specificity, (iv) potency, and (v) a potentially safe and selective knockdown of the targeted cells. However, the problem lies within the formulation and delivery of RNAi therapeutics including rapid excretion, instability in the bloodstream, poor cellular uptake, and inefficient intracellular release. In an attempt to solve these issues, different types of RNAi therapeutic delivery strategies including multifunctional RNA nanoparticles are being developed. In this mini-review, we will briefly describe some of the current approaches.
Effect of Coconut Water Extract on the Growth and Serum Biochemical Values of Rats Fed Fish Oil Diet (2014)

To justify the safety of ethanolic extract of coconut water (CWE), a study with rats was conducted. Wistar rats fedfish oil diet and rats fed the standard diei of AIN93G groupi were orally administrated 0.8 ml CWE/rat twice per day for 14 days. During experimental period, the behavior and growth of rats were monitored. At the end of experiment, the rats were anaesthetized and the internal organs were taken and measuredfor each weight. Blood was taken from the hearth and then analyzed for serum biochemical values and TBARS. The results, no adverse effects of CWE administration were observed as evaluated by growth pattern, food intake and feces appearance. Serum biochemical values and weight of internal organs of CWE receiving rats were comparable to those of untreated control. SeruniTBARS value of rats fedfish oil was significantly higher than that of those ed standard diet, however, oral administratibn of CWE did not significantly decreaie serum TBARS
Drug Delivery Systems (1995)

Drug delivery technologies represent a vast and vital area of Research and Development. The demand for innovative drug delivery systems continues to grow, and this growth continues to drive new developments. Building on the foundation provided by the first edition, Drug Delivery Systems, Second Edition covers the latest developments in both
A 100-g laboratory corn wet-milling procedure. (1996)

Cereal Chem. 73(1):54-57 A 100-g laboratory corn wet-milling procedure was developed in formed during the same week, and 0.60% when replicates were performed order to reduce sample size and labor time requirements for determining weekly during the course of a year. In a properly equipped laboratory, the milling characteristics of corn samples. The procedure gives starch the procedure can be performed at the rate of 40 samples per week using yields statistically similar to those of a 1-kg laboratory procedure with a three trained personnel. standard deviation in replicates of 0.36% when the replicates were perThe feasibility of corn wet-milling facilities processing specific hybrids of yellow dent corn rather than mixed hybrid commodity corn has been enhanced by the use of biotechnology and genetic engineering in corn hybrid development. Identification of better wet-milling hybrids has been limited, in part, by the slow speed of widely used analytical milling techniques. The milling quality of corn (millability) can be evaluated by using laboratory-scale milling procedures (Dimler et al 1944,
Programmable self-assembly in a thousand-robot swarm (2014)

Self-assembly enables nature to build complex forms, from multicellular organisms to complex animal structures such as flocks of birds, through the interaction of vast numbers of limited and unreliable individuals. Creating this ability in engineered systems poses challenges in the design of both algorithms and physical systems that can operate at such scales. We report a system that demonstrates programmable self-assembly of complex two-dimensional shapes with a thousand-robot swarm. This was enabled by creating autonomous robots designed to operate in large groups and to cooperate through local interactions and by developing a collective algorithm for shape formation that is highly robust to the variability and error characteristic of large-scale decentralized systems. This work advances the aim of creating artificial swarms with the capabilities of natural ones.
How Do Glucocorticoids Influence Stress Responses? Integrating Permissive, Suppressive, Stimulatory, and Preparative Actions* (2000)

The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stress-response or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole.
A Dual Phosphoinositide-3-Kinase α/mTOR Inhibitor Cooperates with Blockade of Epidermal Growth Factor Receptor in PTEN -Mutant Glioma (2007)

We have shown previously that blockade of epidermal growth factor receptor (EGFR) cooperates with a pan-selective inhibitor of phosphoinositide-3-kinase (PI3K) in EGFR-driven glioma. In this communication, we tested EGFR-driven glioma differing in PTEN status, treating with the EGFR inhibitor erlotinib and a novel dual inhibitor of PI3Kalpha and mTOR (PI-103). Erlotinib blocked proliferation only in PTEN(wt) cells expressing EGFR. Although erlotinib monotherapy showed little effect in PTEN(mt) glioma, PI-103 greatly augmented the antiproliferative efficacy of erlotinib in this setting. To address the importance of PI3K blockade, we showed in PTEN(mt) glioma that combining PI-103 and erlotinib was superior to either monotherapy or to therapy combining erlotinib with either rapamycin (an inhibitor of mTOR) or PIK-90 (an inhibitor of PI3Kalpha). These experiments show that a dual inhibitor of PI3Kalpha and mTOR augments the activity of EGFR blockade, offering a mechanistic rationale for targeting EGFR, PI3Kalpha, and mTOR in the treatment of EGFR-driven, PTEN-mutant glioma.
Proactive Use of Highway Recorded Data via an Event Data Recorder (EDR) to Achieve Nationwide Seat Belt Usage in the 90th Percentile by 2002 (1999)

Automobiles have been in existence for over a hundred years (1898-1999). Today, we have over two hundred and fourteen million in America alone, and six hundred and ninety million worldwide. Nationwide, forty-seven million vehicles are continually in-motion during daytime usage. Within twenty years these numbers are expected to double. Last year, twenty-four million vehicles were involved in a crash or accident. Over 40,000 people died (115 daily) and the total economic cost is estimated at $150 billion annually. (Blincoe 1996) The personal, social, and economic costs of motor vehicle crashes include pain and suffering; direct costs sustained by the injured persons and their insurers; indirect costs to taxpayers for health care and public assistance; and for many victims, a lower standard of living and quality of life. During the past two decades, motor vehicles accounted for over 90 percent of all transportation fatalities, and an even larger percentage of accidents and injuries. Our increasingly mobile society exposes all age groups to the risks of crashes, as passengers, as drivers, and as pedestrians. The automobile is essential for the style of life we demand, and yet, motor vehicle crashes remain a major public health problem. In contemporary society automobiles play an indispensable role in transporting people and goods, and yet, the health care cost of motor vehicle crashes is a national financial burden that must and can be reduced. Worldwide, research and development is underway into systems that link highway infrastructure and telecommunications using emerging technologies via computers, electronics, and advanced sensing systems. While this paper will propose a highway safety counter-measure it will do so after reviewing the policy issues that created the current circumstances connected with occupant safety. Without this review it be impossible to understand the simplicity of the proposed counter-measure. This paper will identify methods for expanding the use of recorded data on highways to improve transportation safety by providing something that has yet to be achieved in the history of the automobile—a simple transportation safety technology capable of reducing fatalities of comparable magnitude. Thus, the primary objective is to technically explain this highway safety countermeasure, designated Seat Belt Event Data Recorder (SB-EDR). A device combining occupant sensing technologies to encourage and monitor seat belt usage within an Event Data Recorder (EDR) is what is required to produce a large change in United States and worldwide auto fatalities. Such a device would do so by achieving something that has eluded motorists to date-- the widespread use of seat belts twenty-four hours a day.