gebhart/patrepeval huggingface dataset:
The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein (2000)

Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples were collected. The high-fat test was associated with an increase in plasma triglyceride and kallikrein concentrations and postprandial FVII activation (p<0.001). Plasma kallikrein was strongly associated with triglycerides in fasting and non-fasting samples (r2=0.74-0.87, p<0.0001), suggesting that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride-rich lipoproteins activate prokallikrein postprandially, which might form an important initial event in FVII activation after consumption of high-fat meals.
Long Term Chrysotherapy (1979)

The frequency and incidence of certain forms of toxicity in patients receiving long term chrysotherapy for rheumatoid arthritis have been reliably calculated for defined, sequential time periods. Ninety-four patients who received 100 courses of gold therapy for a total treatment period of 134.4 patient-years were followed at one gold therapy clinic. For the period of 0--3 months, the incidences of rash, mouth ulcer, and proteinuria were 9.8, 4.0, and 1.8 episodes per 10,000 patients/month, respectively. However, the incidence of these forms of toxicity decreased progressively in subsequent time periods of continued chrysotherapy. No similar decrease was noted in the incidence of thrombocytopenia, but it would appear that the methodology used in monitoring significantly affects the incidence of clinically important thrombocytopenia. No predictive correlates could be determined for patients who had gone into sustained remission. However, the data strongly suggest that patients who improve within 6 months may continue chrysotherapy for at least up to 3 years with an increasing margin of safety for mucocutaneous and renal toxicity.
Uncovering the complexities of retroviral ribonuclease H reveals its potential as a therapeutic target. (2003)

Successful long-term management of HIV infection will require targeted inhibition of multiple steps essential for virus replication. Currently, both nucleoside- and nonnucleoside-based inhibitors of DNA polymerase function, in combination with antagonists of HIV protease, have been shown to be clinically beneficial. However, it is clear that RNase H activity of the multifunctional HIV-1 reverse transcriptase (RT) is absolutely required for completion of retroviral DNA synthesis, thereby rendering this function an attractive target for drug development. Although generally viewed as a sequence-independent activity, highly precise RNase H cleavage is required in order to remove the RNA primers of (-) and (+) strand DNA synthesis (a host-derived tRNA and the polypurine tract, respectively), thereby preserving the ends of linear DNA and facilitating integration. The availability of highly purified, recombinant RT/RNase H has allowed a thorough dissection of these multiple events and their potential for therapeutic intervention. Our current understanding of retroviral RNase H function and the status of small molecule inhibitors are the focus of this review.
Glycoengineered Acid α-Glucosidase With Improved Efficacy at Correcting the Metabolic Aberrations and Motor Function Deficits in a Mouse Model of Pompe Disease (2009)

Improving the delivery of therapeutics to disease-affected tissues can increase their efficacy and safety. Here, we show that chemical conjugation of a synthetic oligosaccharide harboring mannose 6-phosphate (M6P) residues onto recombinant human acid alpha-glucosidase (rhGAA) via oxime chemistry significantly improved its affinity for the cation-independent mannose 6-phosphate receptor (CI-MPR) and subsequent uptake by muscle cells. Administration of the carbohydrate-remodeled enzyme (oxime-neo-rhGAA) into Pompe mice resulted in an approximately fivefold higher clearance of lysosomal glycogen in muscles when compared to the unmodified counterpart. Importantly, treatment of immunotolerized Pompe mice with oxime-neo-rhGAA translated to greater improvements in muscle function and strength. Treating older, symptomatic Pompe mice also reduced tissue glycogen levels but provided only modest improvements in motor function. Examination of the muscle pathology suggested that the poor response in the older animals might have been due to a reduced regenerative capacity of the skeletal muscles. These findings lend support to early therapeutic intervention with a targeted enzyme as important considerations in the management of Pompe disease.
Cellular evidence for selfish spermatogonial selection in aged human testes (2013)

Owing to a recent trend for delayed paternity, the genomic integrity of spermatozoa of older men has become a focus of increased interest. Older fathers are at higher risk for their children to be born with several monogenic conditions collectively termed paternal age effect (PAE) disorders, which include achondroplasia, Apert syndrome and Costello syndrome. These disorders are caused by specific mutations originating almost exclusively from the male germline, in genes encoding components of the tyrosine kinase receptor/RAS/MAPK signalling pathway. These particular mutations, occurring randomly during mitotic divisions of spermatogonial stem cells (SSCs), are predicted to confer a selective/growth advantage on the mutant SSC. This selective advantage leads to a clonal expansion of the mutant cells over time, which generates mutant spermatozoa at levels significantly above the background mutation rate. This phenomenon, termed selfish spermatogonial selection, is likely to occur in all men. In rare cases, probably because of additional mutational events, selfish spermatogonial selection may lead to spermatocytic seminoma. The studies that initially predicted the clonal nature of selfish spermatogonial selection were based on DNA analysis, rather than the visualization of mutant clones in intact testes. In a recent study that aimed to identify these clones directly, we stained serial sections of fixed testes for expression of melanoma antigen family A4 (MAGEA4), a marker of spermatogonia. A subset of seminiferous tubules with an appearance and distribution compatible with the predicted mutant clones were identified. In these tubules, termed 'immunopositive tubules', there is an increased density of spermatogonia positive for markers related to selfish selection (FGFR3) and SSC self-renewal (phosphorylated AKT). Here we detail the properties of the immunopositive tubules and how they relate to the predicted mutant clones, as well as discussing the utility of identifying the potential cellular source of PAE mutations.
Stability and Polymerase Recognition of Pyridine Nucleobase Analogues: Role of Minor‐Groove H‐Bond Acceptors (2006)

In the groove: In an effort to develop unnatural base pairs, pyridyl nucleoside analogues were synthesized and characterized (see structures). An α-glycosidic nitrogen atom provides an H-bond acceptor that does not significantly facilitate pairing with natural nucleobases. However, it forms minor-groove H-bonds with water molecules and DNA polymerases that optimize the stability and replication, respectively, of the unnatural base pair.
Biomarkers in Diagnosis of Pancreatic Carcinoma in Fine-Needle Aspirates (2006)

This study was undertaken to determine whether recently identified proteins could be translated to clinical practice as markers to distinguish pancreatic adenocarcinoma from chronic pancreatitis on fine-needle aspirate (FNA) samples. Resected pancreatic tissue sections (n = 40) and FNA samples (n = 65) were stained for clusterin-beta, MUC4, survivin, and mesothelin. For each biomarker, the staining patterns in adenocarcinoma and in reactive ductal epithelium were evaluated and compared. Clusterin-beta stained reactive ductal epithelium significantly more frequently than pancreatic adenocarcinoma (P < .001). In comparison, MUC4 and mesothelin were expressed more frequently in pancreatic adenocarcinoma on tissue sections. Positive staining for MUC4 (91% vs 0%; P < .001) and mesothelin (62% vs 0%; P = .01) and absence of staining for clusterin-beta (90% vs 7%; P < .001) were noted significantly more frequently in adenocarcinoma cells than in reactive cells in FNA samples. Clusterin-beta and MUC4 can help distinguish reactive ductal epithelial cells from the cells of pancreatic adenocarcinoma in FNA samples.
Recent Applications of RNAi in Mammalian Systems (2004)

RNAi is a powerful cellular mechanism that involves targeted destruction of mRNAs. Although the phenomenon was first discovered in plants and lower eukaryotic organisms, it was later discovered as an important genetic regulatory mechanism in mammalian cells. RNAi is triggered by double stranded RNAs that are cleaved into short 21-23 base pair duplexes by an RNAse III type enzyme called Dicer. The short RNAs, termed small interfering RNAs (siRNAs), act as triggers for targeted RNA degradation. One of the two strands is selectively incorporated into a complex of proteins called the RNA induced silencing complex, or RISC. The incorporated small RNA guides the complex to the complementary target sequence, and this event is followed by endonucleolytic cleavage of the target and recycling of RISC. In mammalian cells, siRNAs do not activate interferon pathway genes, thereby making these powerful tools for sequence specific knockdown of RNAs. In this article we review the methods for programming mammalian cells with siRNAs, and overview a number of applications ranging from targeting oncogenes to inhibiting viral replication. The article also summarizes some important biological conclusions that can be drawn from selective downregulation of certain mRNA targets and addresses potential uses of RNAi as a new therapeutic modality.
En la cuerda floja (2016)

La ciencia va atesorando descubrimientos cruciales sobre la vida privada de los orangutanes, mientras el esquivo primate de pelaje rojizo se enfrenta a un futuro incierto
Molecular Modelling of Anthraquinone‐oligodeoxynucleotide Conjugates (1996)

Molecular modelling studies show that an anthraquinone attached to an oligodeoxynucleotide is forced to adopt a perpendicular orientation of intercalation, and that the site of the intercalation is found at the triplex-duplex junction. In addition, the optimum length for the linking-chain between the anthraquinone and the 5′ phosphate of the oligodeoxynucleotide is five carbons.
A Highly Efficient Method for Site-Specific Modification of Unprotected Peptides after Chemical Synthesis (2000)

We have developed a highly efficient method for the site-specific attachment of biophysical probes to unprotected peptides after chemical synthesis. This methodology takes advantage of the selective reactivity of an N-methylaminooxy amino acid that is appropriately protected for direct incorporation during solid-phase peptide synthesis. The functional N-methylaminooxy group is unmasked using normal peptide cleavage conditions and is capable of selective reaction with activated N-hydroxysuccinimide esters in the presence of cysteine, lysine and the amino terminus, as demonstrated in model peptides and test proteins. Selective labeling can be accomplished after synthesis using commercially available or chemically sensitive probes. This technology is compatible with the synthesis of Cα-thioester-containing peptides and amide-forming ligations, required steps for the synthesis of proteins by either total chemical synthesis or expressed protein ligation. The N-methylaminooxy amino acid can be introduced into different sites by parallel peptide synthesis to generate a polypeptide analogue family with each member possessing a single specifically labeled site. This enables the synthesis of optimized biosensors through combinatorial screening of different attachment sites for maximal response and minimal perturbation of biological activity.
Hemolytic-uremic syndrome associated with gemcitabine: a case report and review of literature. (2005)

With multiple reports of hemolytic uremic syndrome complicating gemcitabine therapy, it is imperative that clinicians heighten their awareness of this potentially lethal complication.
The ESP DES-CBC Transform (1995)

This document describes the DES-CBC security transform for the IP Encapsulating Security Payload (ESP).
An RT-PCR assay for the enzyme activity of reverse transcriptase capable of detecting single virions (1993)

Journal Article An RT-PCR assay for the enzyme activity of reverse transcriptase capable of detecting single virions Get access Jonathan Silver, Jonathan Silver Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas Maudru, Thomas Maudru Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Kazunobu Fujita, Kazunobu Fujita Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Roy Repaske Roy Repaske Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesda, MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 21, Issue 15, 25 July 1993, Pages 3593–3594, https://doi.org/10.1093/nar/21.15.3593 Published: 25 July 1993 Article history Received: 25 May 1993 Revision received: 20 June 1993 Accepted: 20 June 1993 Published: 25 July 1993
High efficiency aerosol dispersion cell for laser ablation-ICP-MS (2006)

A novel ablation cell for laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was developed. The “high efficiency aerosol dispersion” (HEAD) ablation cell is based on the use of a directed gas flow expansion of the laser generated aerosol at the ablation site and a venturi effect created by two nozzles to extract the aerosol into the main make up gas stream, which finally transports the particles into the ICP. The figures of merit were evaluated based on the ablation of glass SRM NIST 610 using two different cell gases (Ar and He). The investigation of the capabilities of this type of aerosol extraction (using a Nd:YAG laser, λ = 266 nm) demonstrates that a laser generated aerosol can be modified (HEAD effect) by shifting the original particle size distribution towards smaller particle sizes. This effect was obtained for both gases (Ar and He) for increasing cell gas flows and showed an optimum at a flow rate of 100 ml min−1. In comparison with standard cell results, elemental ratios (e.g. U/Th) showed reduced elemental fractionation effects attributed to reduced agglomeration and, therefore, an improved vaporization of the aerosol within the ICP. Most importantly, stability and reproducibility of the ion-signals were significantly improved without compromising sensitivity. In addition to the glass analysis, the HEAD ablation cell was also used for the ablation of brass samples, as this matrix is known to show pronounced elemental fractionation effects due to the thermal volatility difference of Cu and Zn. The temporal stability of element ratios (e.g. Cu/Zn) achievable using such an extraction approach (5%) was significantly improved in comparison with previously reported Cu/Zn ratios (30%) measured using standard cell configurations.
Spinal Cord Ischemia (2000)

Spinal cord ischemia caused by aortic arch plus left subclavian artery cross-clamping provides a mouse model useful for the study of spinal cord injury and of potential relevance to the complications following thoracoabdominal aortic surgery in humans.
NCX-4016, a nitro-derivative of aspirin, inhibits EGFR and STAT3 signaling and mdulates Bcl-2 proteins in cisplatin-resistant human ovarian cancer cells and xenografts (2008)

We have previously reported the inhibitory effect of NCX-4016, a nitro derivative of aspirin, on the proliferation of cisplatin-resistant human ovarian cancer cells, in vitro (Bratasz et al., Proc Natl Acad Sci USA 2006; 103:3914-9). In this report we present the results of our study on the mechanistic aspects of drug action including the molecular and signaling pathways involved in an in vitro cell line, as well as in a murine tumor xenograft. We report, for the first time, that NCX-4016 significantly inhibited the growth of cisplatin-resistant human ovarian cancer xenografts in mice. We observed that the inhibitory effect of NCX-4016 on cell proliferation was associated with G(1) phase cell cycle arrest with increased activity of p53, p21 and p27 proteins. NCX-4016 modulated the Bcl-2 family of proteins, and induced apoptosis by activating Bax and cytochrome c release in a time-dependent manner. In addition, NCX-4016 selectively down-regulated the phosphorylated forms of EGFR (Tyr845, Tyr992), pAkt (Ser473, Thr305), and STAT3 (Tyr705, Ser727), in vitro and in vivo. Taken together, the results clearly suggested that NCX-4016 causes significant induction of cell cycle arrest and apoptosis in cisplatin-resistant human ovarian cancer cells via down-regulation of EGFR/PI3K/STAT3 signaling and modulation of Bcl-2 family proteins. Thus, NCX-4016 appears to be a potential therapeutic agent for treating recurrent human ovarian carcinoma.
TGF-&#946; Pathway as a Potential Target in Neurodegeneration and Alzheimers (2006)

Alzheimer's disease (AD) is a fatal neurodegenerative disease characterized by the loss of large numbers of forebrain neurons. There are currently no effective AD treatments available and the cause of the disease is unknown in the majority of cases. Because normal neuronal maintenance and survival depends on stimulation of key signaling pathways by a number of neurotrophic factors it has been postulated that reduced signaling by or expression of these factors may promote neurodegeneration. Growing evidence suggests that the transforming growth factor-beta (TGF-beta) signaling pathway may be one such neurotrophic pathway that meets important protective and survival roles in neurons. Here I explore this evidence and discuss the pathway as a potential target for the treatment of neurodegeneration and AD.
Reversible Sodium Ion Insertion in Single Crystalline Manganese Oxide Nanowires with Long Cycle Life (2011)

Single crystalline Na4Mn9O18 nanowires are prepared with a polymer-pyrolysis method. This material shows a high, reversible sodium ion insertion/extraction capacity, excellent cycling ability, and promising rate capability for sodium-ion battery applications.
A single probe spatial averaging technique for guided waves and its application to surface wave rail inspection (2007)

The nondestructive testing of structures using guided waves requires systems with high mode selectivity. Usually this is achieved with relatively complex probes comprising multiple transducer rings or arrays. For the rapid inspection of very long structures with only partial access to the waveguide, this may not be a viable solution. In this paper we present a very flexible alternative whereby a simple robust probe is scanned along the wave guide, and the acquired scan data is used for customizing the mode selectivity at the postprocessing stage. The characteristics of this spatial averaging method are discussed using a simple analytical model and compared to an existing linear array technique. The mode selectivity is found to be mainly limited by the uncertainty of the phase velocity assumed for the mode of interest. The method was successfully applied to surface wave rail inspection and was found to suppress unwanted modes very efficiently.
Optimized Directional Lifting with Reduced Complexity (2008)

The direction-adaptive discrete wavelet transform (DADWT) proves to be a very competitive alternative in scalable wavelet-based compression of images, yielding impressive compression performance gains in comparison to the classical DWT. A major limitation of DADWT though stems from its complexity, requiring an exhaustive search for the optimum prediction direction to be employed in the directional lifting process. This paper proposes a novel algorithm to lower the complexity of the DADWT by predicting the optimal prediction direction using a gradient-based technique. The algorithm is developed based on a mathematical model of the prediction errors generated via directional lifting of an input wedge image. The proposed approach avoids a time-consuming exhaustive search and yet the prediction step remains very simple and fast. It is shown that the proposed algorithm brings a complexity-reduction factor of 11/4 for almost no penalty in the prediction accuracy.
Demonstrating Electron Transfer and Nanotechnology: A Natural Dye-Sensitized Nanocrystalline Energy Converter (1998)

A unique solar cell fabrication procedure has been developed using natural anthocyanin dyes extracted from berries. It can be reproduced with a minimum amount of resources in order to provide an interdisciplinary approach for lower-division undergraduate students learning the basic principles of biological extraction, physical chemistry, and spectroscopy as well as environmental science and electron transfer. Electron transfer is the basis of the energetics that drives the processes of life on Earth, occurring in both the mitochondrial membranes of living cells and in the thylakoid membranes of photosynthetic cells of green plants and algae (1). Although we depend on the petroleum and agricultural products of this electron and energy transfer, one of the greatest challenges of the 21st century is that we have yet to create devices that can be used to tap directly into the ultimate source of this energy on an economic scale. An experimental lab procedure was therefore created in order to illustrate the connections between natural and man-made solar conversion within a three-hour lab period.
SP 800-94. Guide to Intrusion Detection and Prevention Systems (IDPS) (2007)

The National Institute of Standards and Technology (NIST) developed this document in furtherance of its statutory responsibilities under the Federal Information Security Management Act (FISMA) of 2002, Public Law 107-347. This publication seeks to assist organizations in understanding intrusion detection system (IDS) and intrusion prevention system (IPS) technologies and in designing, implementing, configuring, securing, monitoring, and maintaining intrusion detection and prevention systems (IDPS). It provides practical, real-world guidance for each of four classes of IDPS: network-based, wireless, network behavior analysis software, and host-based. The publication also provides an overview of complementary technologies that can detect intrusions, such as security information and event management software. It focuses on enterprise IDPS, but most of the information in the publication is also applicable to standalone and small-scale IDPS deployments.