gebhart/patrepeval huggingface dataset:
Instrument for Real-Time Digital Nucleic Acid Amplification on Custom Microfluidic Devices (2016)

Nucleic acid amplification tests that are coupled with a digital readout enable the absolute quantification of single molecules, even at ultralow concentrations. Digital methods are robust, versatile and compatible with many amplification chemistries including isothermal amplification, making them particularly invaluable to assays that require sensitive detection, such as the quantification of viral load in occult infections or detection of sparse amounts of DNA from forensic samples. A number of microfluidic platforms are being developed for carrying out digital amplification. However, the mechanistic investigation and optimization of digital assays has been limited by the lack of real-time kinetic information about which factors affect the digital efficiency and analytical sensitivity of a reaction. Commercially available instruments that are capable of tracking digital reactions in real-time are restricted to only a small number of device types and sample-preparation strategies. Thus, most researchers who wish to develop, study, or optimize digital assays rely on the rate of the amplification reaction when performed in a bulk experiment, which is now recognized as an unreliable predictor of digital efficiency. To expand our ability to study how digital reactions proceed in real-time and enable us to optimize both the digital efficiency and analytical sensitivity of digital assays, we built a custom large-format digital real-time amplification instrument that can accommodate a wide variety of devices, amplification chemistries and sample-handling conditions. Herein, we validate this instrument, we provide detailed schematics that will enable others to build their own custom instruments, and we include a complete custom software suite to collect and analyze the data retrieved from the instrument. We believe assay optimizations enabled by this instrument will improve the current limits of nucleic acid detection and quantification, improving our fundamental understanding of single-molecule reactions and providing advancements in practical applications such as medical diagnostics, forensics and environmental sampling.
Hepatitis C virus (HCV) circulates as a population of different but closely related genomes: quasispecies nature of HCV genome distribution (1992)

Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified products demonstrated that the degree of heterogeneity of two well-conserved regions of the hepatitis C virus (HCV) genome within individual plasma samples from a single patient was consistent with a quasispecies structure of HCV genomic RNA. About half of circulating RNA molecules were identical, while the remaining consisted of a spectrum of mutants differing from each other in one to four nucleotides. Mutant sequence diversity ranged from silent mutations to appearance of in-frame stop codons and included both conservative and nonconservative amino acid substitutions. From the relative proportion of essentially defective sequences, we estimated that most circulating particles should contain defective genomes. These observations might have important implications in the physiopathology of HCV infection and underline the need for a population-based approach when one is analyzing HCV genomes.
Interleukin‐10 in viral diseases and cancer: exiting the labyrinth? (2004)

Interleukin-10 (IL-10) is unique among cytokines, as it is considered both as a potent immunostimulatory and immunosuppressive factor. This complex biology has been particularly challenging when trying to define the useful or harmful role of IL-10 in chronic viral diseases and cancer. In the present review, we emphasize how these multiple roles define IL-10 as an adaptive molecule, constantly tuning the host response against dangerous and resourceful pathogens.
A Macrocyclic Calpain Inhibitor Slows the Development of Inherited Cortical Cataracts in a Sheep Model (2012)

Purpose.: We used sheep with an autosomal dominant gene for cortical cataract as an animal model to evaluate novel macrocyclic calpain inhibitors with potential for the medical treatment of human cataract. Methods.: The macrocyclic aldehyde, CAT811, identified previously as a calpain inhibitor that prevents calcium-induced opacification in cultured sheep lenses, was tested for its ability to protect cytoskeletal proteins from calpain proteolysis. CAT811 and its alcohol analogue, CAT505, were formulated separately into ointments, and each was applied twice daily to the right eye of sheep with early cataracts for five months. Progress of cataracts in the sheep was determined by ophthalmologic examination and comparison with a matched sample of sheep treated similarly with ointment that did not contain the active ingredient. Results.: The novel macrocyclic aldehyde, CAT811, was able to inhibit calpain proteolysis of lens cytoskeletal proteins at micromolar concentrations. When applied topically to the eyes of sheep, CAT811 was able to slow cataract development by 27% in the initial three months of treatment (P < 0.05). Its alcohol analogue, CAT505, was not able to slow cataractogenesis significantly. Conclusions.: The inherited sheep cataract provides a reproducible model of cortical cataract over a time scale of several months. The data reported here, using this model, demonstrated the potential of the macrocyclic calpain inhibitor, CAT811, to act as a therapeutic for treatment of cortical cataract.
Studies on the effects of laminin, E-8 fragment of laminin and synthetic laminin peptides PA22-2 and YIGSR on matrix metalloproteinases and tissue inhibitor of metalloproteinase expression. (1994)

These findings suggest that proteinases present in the Engelbreth-Holm-Swarm laminin may account for most, if not all, of the observed laminin-mediated increase in type IV collagenolytic activity. However, the PA22-2-mediated increase in type IV collagenolytic activity of the A-2058 melanoma line remains to be elucidated.
Mat-8, a Novel Phospholemman-like Protein Expressed in Human Breast Tumors, Induces a Chloride Conductance in Xenopus Oocytes (1995)

We recently identified a novel 8-kDa transmembrane protein, Mat-8, that is expressed in a subset of murine breast tumors. We have now cloned a cDNA encoding the human version of Mat-8 and show that it is expressed both in primary human breast tumors and in human breast tumor cell lines. The extracellular and transmembrane domains of Mat-8 are homologous to those of phospholemman (PLM), the major plasmalemmal substrate for cAMP-dependent protein kinase and protein kinase C in several different tissues. PLM, which induces chloride currents when expressed in Xenopus oocytes, contains consensus phosphorylation sites for both cAMP-dependent protein kinase A and protein kinase C in its cytoplasmic domain. In contrast, the cytoplasmic domain of Mat-8 contains no such consensus phosphorylation sites and is, in fact, unrelated to the cytoplasmic domain of PLM. RNA blot analysis reveals that Mat-8 and PLM exhibit distinct tissue-specific patterns of expression. We show that expression of Mat-8 in Xenopus oocytes induces hyperpolarization-activated chloride currents similar to those induced by PLM expression. These findings suggest that Mat-8 and PLM, the products of distinct genes, are related proteins that serve as Cl- channels or Cl- channel regulators but have different roles in cell and organ physiology.
Review Articles: Inflammation in End‐stage Renal Disease: Sources, Consequences, and Therapy (2002)

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in patients with end-stage renal disease (ESRD). Although traditional risk factors are common in ESRD patients, they alone may not be sufficient to account for the high prevalence of CVD in this condition. Recent evidence demonstrates that chronic inflammation, a nontraditional risk factor which is commonly observed in ESRD patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. The causes of inflammation in ESRD are multifactorial and, while it may reflect underlying CVD, an acute-phase reaction may also be a direct cause of vascular injury by several pathogenetic mechanisms. Available data suggest that proinflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. Thus it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. Recent evidence has demonstrated strong associations between inflammation and both increased oxidative stress and endothelial dysfunction in ESRD patients. As there is not yet any recognized, or even proposed, treatment for ESRD patients with chronic inflammation, it would be of obvious interest to study the long-term effect of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in these patients.
Sequence Data Analysis Guidebook (1997)

Computers have revolutionized the analysis of sequencing data. It is unlikely that any sequencing projects have been performed in the last few years without the aid of computers. Recently their role h
Throughput enhancement in TDMA through carrier interferometry pulse shaping (2002)

This paper introduces a novel TDMA scheme that provides enhanced throughput by employing carrier interferometry pulse shapes (CI pulse shapes). At the transmitter, CI pulse shapes are created from the superposition of N carriers, which generates a short mainlobe (pulse) in time. CI pulse shapes are positioned both orthogonally and pseudo-orthogonally in time, enabling the introduction of additional bits into a TDMA burst. Specifically, up to a 100% increase in throughput can be achieved. At the receiver, a novel TDMA detector is deployed where: the pulse shape is broken down into its frequency components and optimally recombined to create frequency diversity benefits. Simulations performed over hilly terrain (HT) and typical urban (TU) GSM channel models indicate that, with a 100% increase in throughput, the proposed system offers up to 6.5 dB performance gains at probability of error of 10/sup -2/ relative to a standard GSM system employing a decision feedback receiver.
Generation of an inducible and optimized piggyBac transposon system† (2007)

Genomic studies in the mouse have been slowed by the lack of transposon-mediated mutagenesis. However, since the resurrection of Sleeping Beauty (SB), the possibility of performing forward genetics in mice has been reinforced. Recently, piggyBac (PB), a functional transposon from insects, was also described to work in mammals. As the activity of PB is higher than that of SB11 and SB12, two hyperactive SB transposases, we have characterized and improved the PB system in mouse ES cells. We have generated a mouse codon-optimized version of the PB transposase coding sequence (CDS) which provides transposition levels greater than the original. We have also found that the promoter sequence predicted in the 5'-terminal repeat of the PB transposon is active in the mammalian context. Finally, we have engineered inducible versions of the optimized piggyBac transposase fused with ERT2. One of them, when induced, provides higher levels of transposition than the native piggyBac CDS, whereas in the absence of induction its activity is indistinguishable from background. We expect that these tools, adaptable to perform mouse-germline mutagenesis, will facilitate the identification of genes involved in pathological and physiological processes, such as cancer or ES cell differentiation.
Antiviral Activity of Nucleoside Analogues against Norovirus (2012)

The antiviral activity of 2'-C-MeC against strains of two different NoV genogroups and the low EC(50) suggest that this nucleoside analogue may be effective against the more prevalent GII NoVs. In the absence of a vaccine, antiviral agents could be an effective intervention to control the spread of human NoV in populations at a high risk for NoV disease.
A frame-based MPEG characteristics extraction tool and its application in video transcoding (2002)

We present a frame-based characteristics extraction tool, which can retrieve meaningful information from MPEG-compressed bitstreams. Taking advantage of the extracted information, we present a general architecture for MPEG video transcoding, which can transcode a given MPEG video bitstream into various MPEG video bitstreams with different characteristics. We also implement an MPEG-2-to-MPEG-4 video transcoder which can not only change the bitstreams' syntax and bitrate but can also encode each semantic video segment as a group of pictures (GOPs), by using the techniques of frame type conversion and video shot boundary detection. Moreover, the proposed transcoder can intelligently select a motion mode for each macroblock of B-VOPs in an MPEG-4 video to avoid some unpredictable artifacts due to mis-selection of the motion mode. This representative application demonstrates the potential usage of such frame-based characteristics.
Invasion of connective tissue by human carcinoma cell lines: requirement for urokinase, urokinase receptor, and interstitial collagenase. (1992)

We have screened six human squamous carcinoma cell lines for their ability to invade connective tissue by using the experimentally modified chorioallantoic membrane of a chick embryo as an in vivo model of invasion. In confirmation of our earlier studies, all the invasive cell lines expressed high levels of surface-bound urokinase type plasminogen activator (uPA). However, some cell lines expressing this activity were not invasive, suggesting that surface uPA, although necessary, was not sufficient. Since in addition to fibronectin, that can be degraded by uPA or plasmin, chorioallantoic membrane connective tissue contains collagen, we examined the profile of collagenases secreted by the various cell lines in search for an activity that would coincide with the invasive phenotype. We found, using gelatin substrate gels, that type IV gelatinase was produced by all six cell types tested, three cell types produced the M(r) 92,000 gelatinase, and three a lower-molecular-weight activity, which we identified by immunoprecipitation with specific antibodies, and by a direct assay of activity, as interstitial collagenase. Only the latter cells were found to be highly invasive. We showed previously that continuous culture in vitro of one of the carcinoma cell lines, HEp3, led to a gradual extinction of their malignant phenotype. To confirm the correlation between invasion and the production of interstitial collagenase, we examined these two functions in cells freshly isolated from a HEp3 tumor and intermittently during passage in vitro. We found that, although the surface uPA activity was slightly diminished in the in vitro grown cultures, it was still within the range of values found in highly malignant cells, suggesting that it is not the reason for the decrease in invasiveness. In contrast, the reduction in interstitial collagenase closely followed the loss of the invasive phenotype; after 30 in vitro passages the cells were almost completely devoid of interstitial collagenase and unable to invade. The decrease in collagenase activity was not the result of an increased tissue inhibitor of metalloproteinases production.
Colorimetric diagnosis of prolonged bluetongue viremia in sheep, using an enzyme-linked oligonucleotide sorbent assay of amplified viral nucleic acids. (1993)

Each of 5 US-origin serotypes of bluetongue virus (BTV) was inoculated into a separate pair of sheep. The duration of each animal's ensuing viremia was monitored, using a BTV serogroup-specific nested polymerase chain reaction (PCR) method and an embryonating chicken egg (ECE) inoculation procedure. Mean duration of viremia was 100 and 38 days for the PCR and ECE methods, respectively. This difference was significant (P < 0.001) and documents a more prolonged viremia in virus-exposed sheep than has been reported. A dual internal oligonucleotide solution hybridization procedure was developed for the rapid (2 hours) colorimetric detection and identification of BTV-specific PCR products. This enzyme-linked oligonucleotide sorbent assay (ELOSA) relied on annealing of separate biotinylated and fluoresceinated probes to the amplified BTV nucleic acid; these complexes were captured on streptavidin-coated microtitration wells and were detected, using a horseradish peroxidase-labeled antifluorescein antibody conjugate. End-point dilution analyses of PCR products indicated that the ELOSA was more sensitive than gel electrophoretic or comparable colorimetric slot-blot hybridization techniques. The BTV PCR-ELOSA system represents a more sensitive and expeditious means of diagnosing BTV-induced viremia than does the ECE procedure currently used. The combination of ELOSA with PCR should facilitate practical application of nucleic acid technology to diagnostic veterinary medicine.
Ultrafast processes and excited state dynamics in conjugated polymers (2008)

The photophysics of a number of conjugated polymers used in organic display applications has been studied using ultrafast techniques. An updated method for measuring the intersystem crossing rate was developed. This has been used to measure the intersystem crossing in a number of conjugated polymers and oligomers. It was found that as expected the intersystem crossing in conjugated polymers is generally very low. The intersystem crossing in a molecule that exhibits dual fluorescence depending on the polarity of the environment was investigated. In polar solvents when the molecule forms a twisted interconnected charge transfer state the intersystem crossing rate was found to be ten times that of the planer locally excited state found in non-polar media. The nature of charge generation in conjugated polymers has also been investigated, it was found that in the prototypical conjugated polymer, polyfluorene, there is no intrinsic charge photogeneration. However, charges can be formed by singlet-singlet annihilation reactions. This is made very efficient in the solid state by the rapid diffusion and migration of excitons. The photophysics of a novel polyfluorene, polyspirobifluorene, was investigated thoroughly; it has been found that the addition of the spiro side group containing electron-donating groups causes a charge transfer state to form between the backbone and the side group. This can act as a reservoir for the emissive singlets, thus giving the polymer a long tail in the fluorescence decay. Finally, ultrafast pump probe spectroscopy was used to investigate on chain migration of excitons in dilute solutions of a ladder type polymer. The migration to the lowest energy segment of the chain shows up as a shift to the red of the photobleaching signal in the pump probe spectrum. This shows that the low energy states become occupied after the initial excitation, as the high energy states become depopulated by the migration, this process taking about 6.2ps.
Macrophage Gene Expression and Foam Cell Formation Are Regulated by Plasminogen (2013)

Our findings demonstrate an unanticipated role of Plg in the regulation of gene expression and cholesterol metabolism by macrophages and identify Plg-mediated regulation of leukotriene B4 as an underlying mechanism.
IL-12p70 Production by Leishmania major -Harboring Human Dendritic Cells Is a CD40/CD40 Ligand-Dependent Process (2000)

Leishmaniasis, a vector-borne parasitic disease, is transmitted during a sandfly blood meal as the parasite is delivered into the dermis. The parasite displays a unique immune evasion mechanism: prevention of IL-12 production within its host cell, the macrophage (i.e., where it differentiates and multiplies). Given the close proximity of skin dendritic cells (DC) to the site of parasite delivery, their critical role in initiating immune responses and the self-healing nature of Leishmania major (Lm) infection, we examined the interaction between myeloid-derived human DC and Lm metacyclic promastigotes (infectious-stage parasites) to model the early "natural" events of infection. We found that DC can take up Lm and, after this internalization, undergo changes in surface phenotype suggesting "maturation". Despite the intracellular location of the parasite and resultant up-regulation of costimulatory and class II molecules, there was no detectable cytokine release by these Lm-harboring DC. However, using intracellular staining and flow cytometry to analyze cytokine production at the single-cell level, we found that Lm-harboring DC, but not monocytes, produce large amounts of IL-12p70 in a CD40 ligand (CD40L)-dependent manner. Finally, DC generated from mononuclear cells from patients with cutaneous leishmaniasis (Lm), once loaded with live metacyclic promastigotes, were found to reactivate autologous primed T lymphocytes and induce a CD40L-dependent IFN-gamma response. Our results link the required CD40/CD40L interactions for healing with DC-derived IL-12p70 production and provide a mechanism to explain the genesis of a protective T cell-mediated response in the face of local immune evasion within the macrophage at the site of Leishmania delivery.
Coherent telescope array with self-homodyne interferometric detection for optical communications (2003)

The performance of a coherent telescope array (CTA) as an optical communications receiving system is analyzed with regards to the benefits and disadvantages in comparison to monolithic large-aperture single telescopes and conventional photon bucket systems, especially in terms of background photons. The bit error rates for differential phase- shift keying (DPSK) and binary pulse position modulation (BPPM) schemes are derived, the former using self-homodyne interferometry as a novel demodulation technique, in which the background photons inter- act incoherently. The possibility of further dividing the receiver's aperture into N.2 smaller subtelescopes is explored, and its adaptability for implementing the N binary phase-shift keying (N-BPSK) technique with optical code division multiplexing (OCDM) is discussed. An N-CTA re- ceiver system with an N-BPSK/OCDM technique is envisioned not only to achieve multiterabit per second data transfer capability, but also to adapt a novel noise suppression technique based on photon correla- tions, which would render a need for expensive and complicated adap- tive optics obsolete. Further combined with significant reduction in weight and overall costs, an N-CTA system with an N-BPSK/OCDM tech- nique could serve in deep space communications as well as in defense to achieve information dominance in the battlefield. © 2003 Society of Photo-