gebhart/patrepeval huggingface dataset:
Intestinal microflora of human infants and current trends for its nutritional modulation (2002)

Diet, among other environmental and genetic factors, is currently recognised to have an important role in health and disease. There is increasing evidence that the human colonic microbiota can contribute positively towards host nutrition and health. As such, dietary modulation has been proposed as important for improved gut health, especially during the highly sensitive stage of infancy. Differences in gut microflora composition and incidence of infection occur between breast- and formula-fed infants. Human milk components that cannot be duplicated in infant formulae could possibly account for these differences. However, various functional food ingredients such as oligosaccharides, prebiotics, proteins and probiotics could effect a beneficial modification in the composition and activities of gut microflora of infants. The aim of the present review is to describe existing knowledge on the composition and metabolic activities of the gastrointestinal microflora of human infants and discuss various possibilities and opportunities for its nutritional modulation.
A pretargeted nanoparticle system for tumor celllabeling (2010)

Nanoparticle-based cancer diagnostics and therapeutics can be significantly enhanced by selective tissue localization, but the strategy can be complicated by the requirement of a targeting ligand conjugated on nanoparticles, that is specific to only one or a limited few types of neoplastic cells, necessitating the development of multiple nanoparticle systems for different diseases. Here, we present a new nanoparticle system that capitalizes on a targeting pretreatment strategy, where a circulating fusion protein (FP) selectively prelabels the targeted cellular epitope, and a biotinylated iron oxide nanoparticle serves as a secondary label that binds to the FP on the target cell. This approach enables a single nanoparticle formulation to be used with any one of existing fusion proteins to bind a variety of target cells. We demonstrated this approach with two fusion proteins against two model cancer cell lines: lymphoma (Ramos) and leukemia (Jurkat), which showed 72.2% and 91.1% positive labeling, respectively. Notably, TEM analysis showed that a large nanoparticle population was endocytosed via attachment to the non-internalizing CD20 epitope.
Human Clinical-Grade Parthenogenetic ESC-Derived Dopaminergic Neurons Recover Locomotive Defects of Nonhuman Primate Models of Parkinson's Disease (2018)

Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. Here, we compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model. We found that the grafts did not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in both groups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstrated that clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical data for China's first ESC-based phase I/IIa clinical study of PD (ClinicalTrials.gov number NCT03119636).
Case 19-2004 (2004)

A boy was seen by his physician because of a one-week history of profound fatigue. He had mild fever, muscle aches, and chest pain but no gastrointestinal or respiratory symptoms. He was taking no medications and had no known allergies. A complete blood count revealed marked eosinophilia but no other abnormalities.
PMM: a parallel architecture for production systems (2003)

The authors investigate methods to speed up the match phase of the execution of production systems. The Rete match algorithm is taken as the basis of the implementation. A partially shared Rete network is proposed for parallel implementation and a hierarchical two-level parallel architecture based on this network is outlined. The proposed architecture achieves significant speedup by reducing the dynamic scheduling overheads of fine-grained jobs in a multiprocessor implementation of the Rete network, while still taking advantage of the sharing of common computations in the network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Very long chain fatty acids in X‐linked adrenoleukodystrophy brain after treatment with Lorenzo's oil (1994)

The fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n-6), eicosopentaenoic (20:5 n-3), and docosahexaenoic (22:6 n-3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n-9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood-brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.
The selective inhibition of thrombin by peptides of boroarginine. (1990)

Peptides containing alpha-aminoboronic acids with neutral side chains are highly effective reaction intermediate analog inhibitors of the serine proteases leukocyte elastase, pancreatic elastase, and chymotrypsin. A protocol has been developed for the synthesis of peptides containing alpha-aminoboronic acids with a basic, 3-guanidinopropyl side chain (boroArg) to extend the range of these compounds to trypsin-like proteases. Ac-(D)Phe-Pro-boroArg-OH, Boc-(D)Phe-Pro-boroArg-OH, and H-(D)Phe-Pro-boroArg-OH were prepared as inhibitors of thrombin based on earlier observations that it has a high affinity for this sequence. All three boronic acids are highly effective, slow-binding inhibitors of thrombin, inhibiting it with final inhibition constants and association rates of: 41 pM, 5.5 x 10(6) M-1 s-1; 3.6 pM, 9.3 x 10(6) M-1 s-1; less than 1 pM, 8.0 x 10(6) M-1 s-1, respectively. Comparison of their binding at equilibrium to thrombin, plasma kallikrein, factor Xa, plasmin, and two-chain tissue plasminogen activator has shown that all three inhibitors have at least 2 orders of magnitude greater affinity for thrombin, with the exception of the acetyl derivative which has a 40-fold greater affinity for thrombin than kallikrein. The boroarginine peptides are effective in inhibiting the action of thrombin in rabbit plasma against its physiological substrates. Activated partial thromboplastin time was significantly prolonged in vitro by all of the inhibitors at concentrations of 50-200 nM. Prolongations of activated partial thromboplastin time were also observed in rabbits after intravenous (40-80 micrograms/kg or subcutaneous (0.20-2 mg/kg) injections of Ac-(D)Phe-Pro-boroArg-OH. Results indicate that this new class of synthetic thrombin inhibitors may be clinically useful as antithrombotic agents.
National Aeronautics and Space Administration 2003 Strategic Plan (2013)

As the 21st century begins to unfold, NASA will focus, with renewed vigor, on the challenges and opportunities before us and on developing the unique capabilities that strengthen America and address our national needs. Our Mission is driven by science, exploration, and discovery, and it will be carried out with a firm commitment to fiscal responsibility. We will study climate change and the natural and human-induced hazards to Earth's ecosystem. We will help to counter the threat of international terrorism by developing technologies that can improve the security and safety of our air transportation system. We will lead the world into a new understanding of our planet, our solar system, and the universe around us, and in so doing, we will begin to understand whether life may have developed elsewhere in the cosmos. This strategic plan lays out our hopes for the future and the important things we seek to accomplish for America. We are privileged to be entrusted with these pursuits and thrilled to be able to carry them out. We invite you to join us on this great adventure. Releasing this strategic plan with our 2004 budget request represents our new commitment to the integration of budget and performance reporting. In this way, we will ensure that strategic priorities are aligned with and influence budget priorities. Our new Integrated Budget and Performance Document, a companion volume to this strategic plan, expands on the goals and objectives presented here and identifies the specific long-term and annual performance measures for which we will be held accountable.
Inhibition of neurite outgrowth on astroglial scars in vitro (1990)

Traumatic injury to the adult mammalian CNS results in the formation of an astroglial-mesenchymal scar that seals the wound site but blocks axonal regeneration in the process. The mechanism that leads to this inhibition of axon outgrowth has been proposed to be either a physical barrier blocking the advancement of the growth cone or chemical factors actively inhibiting axon outgrowth. At present, it is unknown whether one or both of these mechanisms are responsible for the inhibitory nature of the glial scar in vivo. Using a model of CNS trauma that allows for removal of an adult rat glial scar intact on a nitrocellulose support and placement in vitro with the upper surface exposed, we addressed the question of whether the inhibitory effects could be accounted for by chemical components at the scar surface. A purified population of rat hippocampal neurons was seeded onto the scar explants as well as onto explants taken from neonatal rat cerebral cortex, and the extent of neurite outgrowth was compared. We found that the glial scar, at best, stimulates only minimal neurite outgrowth over its surface when compared to the immature environment explanted in the same manner. This growth-inhibitory state cannot merely be explained by neuronotoxic factors or fibroblasts preventing astrocyte-mediated neurite outgrowth. The inhibition is more probably due to the expression of molecules on the surface of the adult scar that either directly inhibit growth cones or inhibit them indirectly by occluding neurite-promoting factors in the extracellular matrix or on the astrocyte surface.
A lipoprotein of Yersinia enterocolitica facilitates ferrioxamine uptake in Escherichia coli (1992)

A cloned fragment of Yersinia enterocolitica DNA complemented the defect in ferrioxamine B uptake of an Escherichia coli fhuE mutant lacking the outer membrane high-affinity transport protein FhuE. Subcloning revealed that a 13.7-kDa outer membrane protein was required for complementation. The amino acid sequence deduced from the nucleotide sequence showed extensive homology to PCPHi, an outer membrane lipoprotein of Haemophilus influenzae. We therefore termed this protein PCPYe. Plasmid-encoded pcpY mediated a low-affinity uptake of ferrioxamine B which may be caused by changes in the permeability of the outer membrane due to an overexpression of this outer membrane protein. A transposon insertion mutant in the plasmid-encoded pcpY gene was transferred into the chromosome of Y. enterocolitica. The resulting mutation had no effect on the high-affinity uptake of ferrioxamine B in Yersinia cells. Using the antibiotic ferrimycin we were able to isolate a Y. enterocolitica mutant lacking the high-affinity outer membrane receptor for ferrioxamine uptake, termed FoxA.
In Vivo Comparison of CHX-DTPA Ligand Isomers in Athymic Mice Bearing Carcinoma Xenografts (1999)

Monoclonal antibodies (MAbs) labeled with radiometallonuclides via metal chelators are being investigated in the laboratory for use in clinical trials. The biodistribution of 111In- and 88Y-labeled antibody (MAb B72.3) using two isomeric forms (CHX-A and CHX-B) of the 2-(p-isothiocyanatobenzyl)-cyclohexyl-DTPA was compared in athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. CHX-(A or B)-125I-DTPA-B72.3 was co-injected in all athymic mice to assess if the chelate conjugation altered the properties of MAb B72.3. In vitro studies demonstrated maintenance of integrity and immunoreactivity for both radioimmunoconjugates. The in vivo analysis, however, indicated major differences between the two isomer forms. In fact, the 88Y-CHX-A-DTPA radioimmunoconjugate demonstrated over the 7-day study period, a more efficient and stable tumor localization as well as a slower blood clearance rate than the CHX-B-DTPA chelate conjugate, suggesting a greater in vivo stability. Differences were also evident in critical normal organ uptake: no significant increase in liver- and spleen- or bone-to-blood ratios was observed when the CHX-A-DTPA chelate was labeled with indium or yttrium. The results described here demonstrate that the CHX-A-DTPA chelate conjugate can be considered more suitable than the CHX-B-DTPA isomer form when radiometallonuclides are coupled to an MAb.
Identification of novel sites in the ovine growth hormone receptor involved in binding hormone and conferring species specificity (1999)

Using site-directed mutagenesis we mutated the extracellular domain of the ovine growth hormone receptor (oGHR) to the corresponding amino acids in the rat GHR at two different sites: site A is between Thr28 and Leu34 and represents a major immunogenic epitope, while site B is between Ser121 and Asp124 and is involved in the interaction of the human GHR with growth hormone (GH). Native and mutant receptors were bacterially expressed and refolded, and then RIA and GH-binding assays were carried out on the purified recombinant proteins. Mutations at the N-terminal site A of oGHR led to greatly reduced binding to bovine GH and, in addition, to significant loss of recognition by a polyclonal antiserum to bovine GHR which recognizes site A as a major epitope. The crystal structure of human GH bound to human GHR did not resolve this extreme N-terminal region of the receptor but our data indicate that the N-terminal loop undertakes a 180 degrees turn bringing it into close proximity to the hormone-binding domain in a fashion analogous to the prolactin receptor. A fourfold decrease in affinity for binding bovine GH was also observed after mutation of site B. However, this change from the ovine sequence to the equivalent sequence in the rat GHR at site B caused a 2.4-fold increase in the affinity of binding to rat GH. Taken together, the changes in binding affinity of the site-B mutant for rat and bovine GH demonstrate that this site is involved in conferring species specificity for binding GH.
A new 94-GHz six-port collision-avoidance radar sensor (2004)

A new 94-GHz collision avoidance radar sensor is proposed. The receiver front-end module is based on a six-port phase/frequency discriminator (SPD). The SPD, composed of four 90/spl deg/ hybrid couplers, is manufactured in a metal block of brass using a computer numerically controlled milling machine. Simulation and measurement S-parameters of the SPD are presented in the frequency band. New SPD computer models are generated and used in the system simulations. Preliminary measurements and system simulations performed to obtain the relative velocity of the target and its distance are presented. Statistical evaluations show an acceptable measurement error of this radar sensor.
Progress toward a Peptidomimetic of Laminin-Derived Pentapeptide YIGSR:  Synthesis of the Unique Tricyclic Core Structure (2002)

The peptide sequence YIGSR, a segment of the basement membrane matrix glycoprotein laminin, has been identified as a key component in tumor cell invasion. Guided by extensive NMR work and de novo design algorithms, a nonpeptide mimetic of this pentapeptide was identified as a lead candidate for synthesis. The target displays the key amino acid side chains from a novel tricyclic scaffold. The first synthesis of this unique scaffold is completed in 11 steps and 7% overall yield.
Flexible Piezoelectric Tactile Sensor Array for Dynamic Three-Axis Force Measurement (2016)

A new flexible piezoelectric tactile sensor array based on polyvinylidene fluoride (PVDF) film is proposed for measuring three-axis dynamic contact force distribution. The array consists of six tactile units arranged as a 3 × 2 matrix with spacing 8 mm between neighbor units. In each unit, a PVDF film is sandwiched between four square-shaped upper electrodes and one square-shaped lower electrode, forming four piezoelectric capacitors. A truncated pyramid bump is located above the four piezoelectric capacitors to improve force transmission. A three-axis contact force transmitted from the top of the bump will lead to the four piezoelectric capacitors underneath undergoing different charge changes, from which the normal and shear components of the force can be calculated. A series of dynamic tests have been carried out by exerting sinusoidal forces with amplitudes ranging from 0 to 0.5 N in the x-axis, 0 to 0.5 N in the y-axis, and 0 to 1.5 N in the z-axis, separately. The tactile units show good sensitivities with 14.93, 14.92, and 6.62 pC/N in the x-, y-, and z-axes, respectively. They can work with good linearity, relatively low coupling effect, high repeatability, and acceptable frequency response in the range of 5-400 Hz to both normal and shear load. In addition, dynamic three-axis force measurement has been conducted for all of the tactile units. The average errors between the applied and calculated forces are 10.68% ± 6.84%. Furthermore, the sensor array can be easily integrated onto a curved surface, such as robotic and prosthetic hands, due to its excellent flexibility.
Using Lone Star Ticks,Amblyomma americanum(Acari: Ixodidae), inin VitroLaboratory Bioassays of Repellents: Dimensions, Duration, and Variability (2011)

The in vitro laboratory bioassay is an important tool in tick repellent discovery and development, with a variety of bioassays used in recent years. Several factors, such as size and configuration of test surfaces and duration of tick exposure, can influence the outcome of bioassays. We tested two tick repellents, N,N-diethyl-3-methyl benzamide (deet) and (-)-isolongifolenone, in seven different bioassays or configurations. All bioassays used ≥4 concentrations of repellent and an ethanol control applied to filter paper against lone star tick nymphs, Amblyomma americanum (L.). Climbing bioassays included a 22 × 1 cm vertical filter paper strip and a 4 × 7 cm vertical filter paper strip plus four modifications of the basic 4 × 7 cm configuration. We used a moving object bioassay (MOB), in which a strip of filter paper treated with test solution was affixed to a rotating heated brass drum and ticks allowed to transfer to the paper. A horizontal bioassay in which ticks were confined between two filter paper discs that had one half treated with repellent was also used. For each bioassay, deet and (-)-isolongifolenone were similarly effective, but in some bioassays ticks were repelled by lower concentrations of both repellents than in other bioassays. The 22 × 1 cm strip proved impractical for regular bioassay use, but showed that a height of 8-9 cm and ~6 min duration were optimal for climbing bioassays. When a loop of treated paper was added to untreated lower portion of the 4 × 7 cm filter paper, as alternative escape for ticks responding to repellents, more ticks were on the loop and lower untreated area of the strip at 10 min (end of the test) than were on the lower untreated area of the basic 4 × 7 cm strip. However, with the ethanol controls more ticks fell from 4 × 7 cm strips with loops than those without loops. Several important behaviors associated with host acquisition (contacting, transferring to and remaining on a moving surface) were recorded in the MOB, but we only found significant differences between treatment and control for the proportion of ticks that transferred to the filter paper and the length of time the ticks remained on paper. The petri dish bioassays lasted longer than other bioassays (2h compared to 10 min for the vertical filter bioassays) and allowed detection of a decline in repellency over time. Individual variation among ticks and fatigue (change in response) in repeatedly tested ticks were assessed in a vertical paper strip bioassay using deet. The responses of ticks tested twice on one day (morning and afternoon) did not differ between tests. However, continued repeated daily testing compromised results. A hiatus of about a week between tests allowed ticks to return to their initial response profiles.
PCR-Based detection of minority point mutations (2004)

The need for detection of minority mutations (i.e., a few mutants within a high excess of wild-type alleles) arises frequently in the field of cancer and molecular genetics. Current mutation detection technologies are limited by several technical factors when it comes to the detection of minority point mutations, including generation of misincorporations by the DNA polymerase during PCR amplification. Primer ligation-mediated PCR methodologies for detection of mutations in an excess wild-type sequences are described, that can be applied for detection of both known and unknown minority point mutations. Furthermore, a new methodology is described, hairpin-PCR, which has the potential to completely eliminate PCR errors from amplified sequences, prior to minority mutation detection. Combination of these technologies can effectively tackle the problem of minority mutation detection, in order to pursue demanding applications such as identification of cancer cells at an early stage, detection of mutations in single cells, identification of minimal residual disease, or investigation of mechanisms of spontaneous mutagenesis.
A cloned human T cell line cytotoxic for autologous and allogeneic B lymphoma cells. (1984)

A human cytotoxic T cell clone (MWS-14) with auto-tumor reactivity was established in serum-free medium in a mixed tumor cell culture by repetitive stimulation with fresh autologous lymphoma cells. This clone and its subclones are of the T3+ T4+ T8- phenotype. They were strongly cytotoxic for the autologous lymphoma cells, whereas autologous PHA blasts were not killed. Analysis of the specificity of MWS-14, MWS-14-30, and MWS-14-34 indicated that these CTL clones were cytotoxic for 7/7 allogeneic lymphoma cells, whereas only 3/23 of normal and non-lymphoma cells were lysed. Blocking studies with monoclonal antibodies directed at MHC class I and class II antigens showed that this preferential, anti-lymphoma reactivity was not directed at HLA determinants. The anti-lymphoma activity is not due to an aspecific susceptibility of the lymphoma cells to lysis. In contrast to CTL clones specific for HLA antigens present on the lymphoma cells, T3 and T4 were not involved in the cytotoxic reaction of MWS-14 against the autologous lymphoma cells. The reactivity of this clone could be blocked by a monoclonal antibody directed at leukocyte function-associated antigen. It can be concluded from these results that these T4+ CTL clones recognize a determinant, which is preferentially expressed on autologous and allogeneic lymphoma cells.