gebhart/patrepeval huggingface dataset:
Structural features that influence the ability of lipid A and its analogs to abolish expression of suppressor T cell activity (1992)

Lipid A preparations derived from the lipopolysaccharides of several gram-negative bacteria, as well as chemically defined synthetic lipid A's and their analogs (both glucosamine mono- and disaccharides), were used to establish the chemical structures required for (i) abolishing the expression of suppressor T cell (Ts) function and (ii) inducing polyclonal activation of B cells. Salmonella minnesota R595 lipid A (diphosphoryl lipid A) possesses both of these activities. Decreasing the number of phosphate groups in lipid A from two to one (monophosphoryl lipid A) as well as decreasing the fatty acyl content, primarily by removing the residue at the 3 position, resulted in a progressive reduction in toxicity; however, these structural modifications did not influence its ability to abolish the expression of Ts function. Reducing the fatty acyl content from five to four (lipid A precursor IVA or Ia) eliminated the capacity to influence Ts function but not to induce polyclonal activation of B cells. None of the monosaccharide analogs of lipid A examined influenced the expression of Ts activity, although some were able to activate B cells polyclonally. Thus, in order to be able to abolish the expression of Ts function, lipid A (i) must be a glucosamine disaccharide, (ii) may have either one or two phosphate groups, and (iii) must have at least five fatty acyl groups. Also, the chain length of the nonhydroxylated fatty acid, as well as the location of acyloxyacyl groups (2' versus 3' position), may play an important role. These findings indicate that the chemical structures responsible for the toxicity of lipid A differ from those that influence its capacity to abolish the expression of Ts function and to induce polyclonal activation of B cells.
Measurement of vertical distribution of isoprene in surface seawater, its chemical fate, and its emission from several phytoplankton monocultures (1995)

Concurrent measurements of isoprene (2-methyl-1,3-butadiene) in seawater together with atmospheric concentrations in the Gulf Stream off the Florida coast were made. Florida Straits surface water concentrations of isoprene varied between 9.8 and 50.8 pmol 1−1. Surface water isoprene concentrations showed a positive correlation with measured chlorophyll fluorescence, consistent with the biogenic origin of this non-methane hydrocarbon. Depth profiles showed a maximum in isoprene concentration similar to that of biological productivity as indicated by chlorophyll fluorescence. Daytime atmospheric mixing ratios of isoprene were never above 11 parts-per-trillion (pptv) and eight of eleven samples taken were below the ~ 5 pptv detection limit. Using an estimated value of the Henry's law constant (KH ~ 3.1) a supersaturation of surface seawater of 2 to 3 orders of magnitude is estimated. Laboratory grown monocultures of several common phytoplankton species showed production of isoprene. Processes controlling the isoprene concentration in the photic zone of the ocean and the marine boundary layer are discussed. A calculation using a simple time dependent photochemical box model confirmed that isoprene is rapidly consumed by its reaction with the OH radical in the marine atmosphere.
TroVax, a recombinant modified vaccinia Ankara virus encoding 5T4: Lessons learned and future development (2010)

There has been renewed interest in developing vaccine and immunotherapy for the treatment of cancer. The oncofetal antigen, 5T4, is a surface glycoprotein that is expressed on a variety of human adenocarcinomas but rarely on normal tissue. 5T4 plays an important role in tumor progression and metastasis. The expression patterns and functional role in the metastatic process suggest that 5T4 is a good target for vaccine development. A modified vaccinia virus Ankara (MVA) encoding human 5T4 (designated TroVax) demonstrated therapeutic effects in murine tumor models and human T cells recognized 5T4 epitopes in an HLA-restricted manner. The TroVax vaccine has subsequently been evaluated in clinical trials targeting patients with colorectal cancer, renal cell carcinoma and hormone refractory prostate cancer. Herein, we review the results of these clinical studies, discuss the lessons learned through these trials and provide some insight into the future development of TroVax as a cancer vaccine.
Vectors for Expression and Secretion of FLAG Epitope-Tagged Proteins in Mammalian Cells (1996)

The FLAG peptide, AspTyrLysAspAspAspAspLys, has been used as an epitope tag in a variety of cell types. The modification of the cytomegalovirus (CMV) promoter containing vector, pCMV5, to create two transient expression vectors designed for secretion and intracellular expression of FLAG-fusion proteins in mammalian cells is described. As a functional test, the bacterial alkaline phosphatase gene was cloned into both vectors, and anti-FLAG monoclonal antibodies were used for detection of FLAG epitope-tagged bacterial alkaline phosphatase in mammalian cells. In addition, secreted bacterial alkaline phosphatase was purified from the extracellular medium by anti-FLAG affinity chromatography.
A massively parallel PicoTiterPlate™ based platform for discrete picoliter‐scale polymerase chain reactions (2003)

We demonstrate successful, simultaneous polymerase chain reaction (PCR) amplification of up to 300 000 discrete reactions in a novel platform, the PicoTiterPlate. In addition to elevated throughput, the PicoTiterPlate based amplifications (PTPCR) can be performed in extremely small volumes: individual reactions volumes are as low as 39.5 pL, with a total 15.3 microL reaction volume for the entire PicoTiterPlate. The bulk PTPCR product can be recovered and assayed with real-time PCR, or discrete PTPCR products can be driven to solid supports, enabling downstream applications such as translation/transcription or sequencing.
Rapid Discovery of Potent siRNA-Containing Lipid Nanoparticles Enabled by Controlled Microfluidic Formulation (2012)

The discovery of potent new materials for in vivo delivery of nucleic acids depends upon successful formulation of the active molecules into a dosage form suitable for the physiological environment. Because of the inefficiencies of current formulation methods, materials are usually first evaluated for in vitro delivery efficacy as simple ionic complexes with the nucleic acids (lipoplexes). The predictive value of such assays, however, has never been systematically studied. Here, for the first time, by developing a microfluidic method that allowed the rapid preparation of high-quality siRNA-containing lipid nanoparticles (LNPs) for a large number of materials, we have shown that gene silencing assays employing lipoplexes result in a high rate of false negatives (~90%) that can largely be avoided through formulation. Seven novel materials with in vivo gene silencing potencies of >90% at a dose of 1.0 mg/kg in mice were discovered. This method will facilitate the discovery of next-generation reagents for LNP-mediated nucleic acid delivery.
Maritime surveillance in the Intracoastal Waterway using networked underwater acoustic sensors integrated with a regional command center (2010)

Underwater passive acoustic directional sensors and Seaweb through-water networked acoustic communications are implemented in the Intracoastal Waterway at Morehead City, North Carolina on the U.S. eastern seaboard. The objective is to demonstrate capability for first-alert protection of a high-value port facility against asymmetric threats that intelligence sources indicate are arriving via watercraft. Battery-powered acoustic sensors are rapidly deployed at widely separated chokepoint locations in shallow 5-10 meter water. These sensors autonomously detect the passage of a maritime vessel and generate a contact report indicating time, location and heading of the target. Seaweb through-water acoustic communications delivers the contact report via a scalable wide-area underwater network including multiple acoustic repeater nodes and a radio/acoustic communications (Racom) gateway buoy. The Racom gateway telemeters the contact report via Iridium satellite communications to an ashore command center with low latency. The in situ acoustic detection is corroborated using shore-based video surveillance to classify the contact as friendly or actionable.
Stromal cells regulate survival of B-lineage leukemic cells during chemotherapy (2000)

Approximately 20% of B-lineage acute lymphoblastic leukemias are not cured by traditional chemotherapy. The possibility was examined that residual leukemic cells that potentially contribute to relapse are harbored in association with fibroblastic stromal cells in the bone marrow. Modulation of cytarabine (Ara-C) and etoposide (VP-16) efficacy by bone marrow stromal cells in vitro was investigated. Stromal cell coculture was shown to sustain the proliferation of B-lineage leukemic cells and to reduce leukemic cell apoptosis when exposed to Ara-C or VP-16. Direct contact with stromal cells was essential for the protection of leukemic cells during chemotherapy, whereas soluble factors had negligible effect. Specifically, signaling mediated through interaction with the stromal cell adhesion molecule VCAM-1 was required to maintain the maximum viability of leukemic cells during Ara-C and VP-16 exposure. In contrast, the interaction of leukemic cells with fibronectin did not confer significant resistance to either chemotherapeutic agent. These observations suggest a role for the bone marrow microenvironment in modulating the response of B-lineage leukemic cells to Ara-C or VP-16, and they indicate specific molecular interactions that may be important in determining the sensitivity of leukemic cells to treatment. (Blood. 2000;96:1926-1932)
Comparison of preservation media for storage of stool samples (1995)

Transportation of clinical samples and long-term recoverability of pathogens are critical to epidemiological studies, particularly when conditions do not permit immediate processing. This study confirms that Cary-Blair medium (CB) is suitable for the preservation of Salmonella and Shigella isolates for more than 2 weeks at 25, 4, or -70 degrees C. Campylobacter jejuni was not recovered after 2 days of storage in CB at 25 degrees C when an inoculum of 12 x 10(8) cells per ml was used. Lower temperatures supported the recovery of this organism for 6 days. When individual pathogens were preserved with stools in CB and incubated at 25, 4, or -70 degrees C, the Salmonella and Shigella concentrations dropped from 12 x 10(8) cells to 1 x 10(3) or 1 x 10(4) cells per ml within 2 days and then remained stable for the rest of the observation period (15 days). C. jejuni survived preservation with stools for 5 to 9 days. The addition of blood and glycerol to CB improved the recoverability of all enteropathogens, particularly C. jejuni, which was consistently detected for 7 to 9 days at the different preservation temperatures used. When trypticase soy broth-glycerol (freezing medium), with or without blood, was used, there was little or no decrease in the Salmonella and Shigella concentrations during 2 weeks of preservation with stools at -70 degrees C. C. jejuni demonstrated a relatively sustained high concentration in Trypticase soy broth-glycerol with 5% blood. The use of defibrinated, laked sheep blood as a long-term freezing medium supported the recovery of low concentrations of Salmonella and Shigella spp. (10(2) to 10(3) cells per ml) for more than 14 weeks. Recovery of C. jejuni was consistent for 7 weeks when an initial concentration of 10(6) cells per ml present in stools. Laked blood provided a simple, sterile, and inexpensive medium for the preservation of individual isolates and clinical samples.
Benefits and risks of live attenuated influenza vaccine in young children. (2010)

Our study suggests that even if LAIV were sometimes used inadvertently in clinical practice in young children for whom it is not indicated, the overall balance of expected benefits and risks would remain favorable.
Neurotoxicity and Memory Deficits Induced by Soluble Low-Molecular-Weight Amyloid- 1-42 Oligomers Are Revealed In Vivo by Using a Novel Animal Model (2012)

Neuronal and synaptic degeneration are the best pathological correlates for memory decline in Alzheimer's disease (AD). Although the accumulation of soluble low-molecular-weight amyloid-β (Aβ) oligomers has been suggested to trigger neurodegeneration in AD, animal models overexpressing or infused with Aβ lack neuronal loss at the onset of memory deficits. Using a novel in vivo approach, we found that repeated hippocampal injections of small soluble Aβ(1-42) oligomers in awake, freely moving mice were able to induce marked neuronal loss, tau hyperphosphorylation, and deficits in hippocampus-dependent memory. The neurotoxicity of small Aβ(1-42) species was observed in vivo as well as in vitro in association with increased caspase-3 activity and reduced levels of the NMDA receptor subunit NR2B. We found that the sequestering agent transthyretin is able to bind the toxic Aβ(1-42) species and attenuated the loss of neurons and memory deficits. Our novel mouse model provides evidence that small, soluble Aβ(1-42) oligomers are able to induce extensive neuronal loss in vivo and initiate a cascade of events that mimic the key neuropathological hallmarks of AD.
Mathematical Modeling of a Cation-Exchange Membrane Containing Two Cations (2008)

Transport phenomena in an ion-exchange membrane containing both and are described using the multicomponent diffusion (extended Stefan–Maxwell) equations. Expressions for macroscopic transport parameters, i.e., conductivity, proton transference number, water electro-osmotic coefficient, and transport parameters characterizing diffusion at zero current, are derived as a function of the binary interaction parameters, , used in the multicomponent transport equations. As experimental data for only four transport properties are available in the literature, the six values cannot be determined in an unequivocal manner. It is in harmony with the data that is large, and linear variations of with are assumed for the other coefficients. Values for the slopes of those linear variations are refined by nonlinear least-square regression on the four experimental transport properties. General governing equations to describe complete transport in the membrane with and are presented, and the model is used with particular boundary conditions to describe the behavior of a membrane used in a electrolyzer. This provides some insights on macroscopic quantities such as the ohmic drop and water transport that are relevant for cell operation.
Birefringence imaging of human skin by polarization-sensitive spectral interferometric optical coherence tomography (2002)

We have developed a spectral interferometric optical coherence tomography (OCT) system with polarization sensitivity that is able to measure a two-dimensional tomographic image by means of one-dimensional mechanical scanning. Our system, which has an axial resolution of 32 mum , calculates the distribution of each element of the Müller matrix of a measured object from 16 OCT images. The OCT system successfully reveals the birefringent nature of human skin tissue.
Expression of MAGE and GAGE in high-grade brain tumors: a potential target for specific immunotherapy and diagnostic markers. (1999)

The mRNA expression of the tumor-associated antigens MAGE and GAGE was examined in 60 high-grade brain tumors. This analysis was performed by using reverse transcription-PCR, Southern blotting, and sequencing. It was demonstrated that, of the eight GAGE genes, GAGE-2 and -7 were expressed in five of seven normal brains. Four groups of tumors--adult glioblastoma multiforme (n = 20), pediatric glioblastoma multiforme (n = 9), medulloblastomas (n = 15), and ependymomas (n = 14)--were analyzed for mRNA expression. The following frequencies were observed: MAGE-1, 0, 0, 13, and 0%, respectively; MAGE-2, 5, 11, 60, and 57%; MAGE-3 & -6, 0, 0, 13, and 0%; GAGE-1, 65, 11, 13, and 43%; and GAGE-3-6 and -8: 75, 78, 47, and 93%, respectively. Two unclassified tumors expressed GAGE-3-6 and -8 only. The absence of GAGE-1 expression in normal brain, its relatively high frequency of expression in high-grade brain tumors, and its unique 3' sequence, suggest it may represent a useful target for specific immunotherapy. The detection method of reverse transcription-PCR and Southern blotting may also be useful for rapid screening of biopsy specimens both for diagnostic purposes and to determine a patient's eligibility for specific immunotherapy.
Analysis of the survival of mature human eosinophils: interleukin-5 prevents apoptosis in mature human eosinophils (1991)

We and other groups have previously shown that interleukin-5 (IL-5) maintained the viability of mature eosinophils in an in vitro liquid culture system. Mature eosinophils did not proliferate but their survival was maintained in the presence of IL-5. Using this culture system, we investigated the mechanism of IL-5-mediated survival. In the absence of human IL-5 (hIL-5) mature eosinophils succumbed after 4 days, while in the presence of hIL-5 they survived up to 10 days. When DNA extracts of cultured eosinophils were analyzed on an agar gel electrophoresis, marked DNA fragmentation was observed in the absence of hIL-5, while no significant DNA fragmentation was observed in the culture with hIL-5 for 48 hours. The DNA fragmentation appeared as early as 6 to 12 hours after hIL-5 deprivation. Concomitantly, IL-5 stimulated total RNA and protein synthesis, but did not induce DNA synthesis in mature eosinophils. Because cycloheximide or actinomycin D impeded the protection of apoptosis by hIL-5, some new RNA and protein synthesis appeared to be required in this phenomena. These findings indicate that IL-5 maintains survival of mature eosinophils with induction of new RNA and protein synthesis, thus leading to the inhibition of apoptosis.
Kinetics of Self-Immolative Degradation in a Linear Polymeric System: Demonstrating the Effect of Chain Length (2013)

We describe here a study demonstrating that the degradation time of self-immolative linear polymers is dependent on chain length. These materials are unique relative to most degradable polymers, in that they undergo end-to-end depolymerization in response to the cleavage of an end-cap. Although one of their cited attributes is a dependence of their degradation time on chain length, no conclusive study has been conducted to demonstrate and study this effect. In this work, using a linear self-immolative polymer backbone derived from alternating 4-hydroxybenzyl alcohol and N,N′-dimethylethylenediamine based spacers, we show that there is a proportional relationship between chain length and depolymerization time. This is first accomplished using a series of oligomers synthesized using a convergent, iterative route and then applied to the polydisperse case on a set of polymers displaying varying molecular weights. We also report the first development and validation of a self-immolative degradation model relating monomer kinetics to polymer degradation and show its application in explaining oligomeric and polymeric degradation profiles.
Polymer–Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs (2016)

Therapeutic nucleic acids hold great promise for the treatment of disease but require vectors for safe and effective delivery. Synthetic nanoparticle vectors composed of poly(β-amino esters) (PBAEs) and nucleic acids have previously demonstrated potential utility for local delivery applications. To expand this potential utility to include systemic delivery of mRNA, hybrid polymer-lipid nanoformulations for systemic delivery to the lungs were developed. Through coformulation of PBAEs with lipid-polyethylene glycol (PEG), mRNA formulations were developed with increased serum stability and increased in vitro potency. The formulations were capable of functional delivery of mRNA to the lungs after intravenous administration in mice. To our knowledge, this is the first report of the systemic administration of mRNA for delivery to the lungs using degradable polymer-lipid nanoparticles.
Regulation of Human Igλ Light Chain Gene Expression by NF-κB (2002)

The human Iglambda enhancer consists of three separated sequence elements that we identified previously by mapping DNase I-hypersensitive regions (HSS) downstream of the C region of the Iglambda L chain genes (HSS-1, HSS-2, and HSS-3). It has been shown by several laboratories that expression of the H chain genes as well as the kappa genes, but not the lambda genes, is dependent on constitutive NF-kappaB proteins present in the nucleus. In this study we show by band-shift experiments, in vivo footprinting, and transient transfection assays that all three hypersensitive sites of the human Iglambda enhancer contain functional NF-kappaB sites that act synergistically on expression. We further show that the chicken lambda enhancer also contains a functional NF-kappaB site but the mouse lambda enhancer contains a mutated, nonfunctional NF-kappaB site that is responsible for its low enhancer activity. It is possible that the inactivating mutation in the mouse Iglambda enhancer was compensated for by an expansion of the Igkappa L chain locus, followed by a contraction of the Iglambda locus in this species.
Rosiglitazone, PPARγ, and Type 2 Diabetes (2010)

Rosiglitazone and other thiazolidinediones are thought to sensitize adipose and other tissues to insulin by activating a molecule called PPARγ. A recent study suggests that the therapeutic effect of rosiglitazone is mediated by its prevention of the phosphorylation of PPARγ.
Accurate calibration of cameras and range imaging sensor: the NPBS method (2003)

A method is presented for modeling and calibration of sensors, to reach an accuracy similar in magnitude to the resolution of the sensors. The authors focus on camera and range image calibration. They show the limitations of existing methods, and present an approach and camera calibration using mathematical B-Spline functions. This method is abbreviated as NPBS (N-Planes B-Spline). It is an extension of the two-planes method, but relies on pure mathematical modeling based on spline approximation theory. The mathematical modeling is combined with a calibration device that enables accurate data acquisition to calibrate a camera and a light plane independently. Experimental results are presented showing accuracy on the determination of a scattered plane.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Two-Stage Wireless Network Emulation (2005)

Testing and deploying mobile wireless networks and applications are very challenging tasks, due to the network size and administration as well as node mobility management. Well known simulation tools provide a more flexible environment but they do not run in real time and they rely on models of the developed system rather than on the system itself. Emulation is a hybrid approach allowing real application and traffic to be run over a simulated network, at the expense of accuracy when the number of nodes is too important. In this paper, emulation is split in two stages: first, the simulation of network conditions is precomputed so that it does not undergo real-time constraints that decrease its accuracy; second, real applications and traffic are run on an emulation platform where the precomputed events are scheduled in soft real-time. This allows the use of accurate models for node mobility, radio signal propagation and communication stacks. An example shows that a simple situation can be simply tested with real applications and traffic while relying on accurate models. The consistency between the simulation results and the emulated conditions is also illustrated.