gebhart/patrepeval huggingface dataset:
The lactoperoxidase system links anion transport to host defense in cystic fibrosis (2006)

Chronic respiratory infections in cystic fibrosis result from CFTR channel mutations but how these impair antibacterial defense is less clear. Airway host defense depends on lactoperoxidase (LPO) that requires thiocyanate (SCN-) to function and epithelia use CFTR to concentrate SCN- at the apical surface. To test whether CFTR mutations result in impaired LPO-mediated host defense, CF epithelial SCN- transport was measured. CF epithelia had significantly lower transport rates and did not accumulate SCN- in the apical compartment. The lower CF [SCN-] did not support LPO antibacterial activity. Modeling of airway LPO activity suggested that reduced transport impairs LPO-mediated defense and cannot be compensated by LPO or H2O2 upregulation.
Effects of hyaluronan on collagen fibrillar matrix contraction by fibroblasts (1994)

Hyaluronan, found in high concentrations in fetal tissues, appears to have a major role in preventing scar formation in fetal wounds. Nevertheless, its role in inhibiting wound contractures associated with scar formation has not been clearly demonstrated. Our current study evaluated the effects of hyaluronan using an in vitro floating collagen fibrillar matrix (CFM) contraction model. The results demonstrated that the contraction of CFM by fibroblasts was significantly reduced when high concentrations (> 1 mg/mL) of hyaluronan were present in the media. This phenomenon is unique to hyaluronan, because chondroitin sulfate was ineffective in this connection. Fibroblast migration and proliferation studies indicated that high concentrations of hyaluronan stimulated cell migration and had no cytotoxic effects. Some possible mechanisms by which high concentrations of hyaluronan reduced CFM contraction by fibroblasts were proposed. Because the viscosity of a hyaluronan solution is much greater than that of chondroitin sulfate, and this increases with concentration, we investigated whether this property in itself was an important factor in inhibiting CFM contraction. No direct correlation was found between the viscosity of glycosaminoglycans and their ability to reduce CFM contraction.
Engineering of Plasmin-Resistant Forms of Streptokinase and Their Production in Bacillus subtilis : Streptokinase with Longer Functional Half-Life (1998)

The short in vivo half-life of streptokinase limits its efficacy as an efficient blood clot-dissolving agent. During the clot-dissolving process, streptokinase is processed to smaller intermediates by plasmin. Two of the major processing sites are Lys59 and Lys386. We engineered two versions of streptokinase with either one of the lysine residues changed to glutamine and a third version with both mutations. These mutant streptokinase proteins (muteins) were produced by secretion with the protease-deficient Bacillus subtilis WB600 as the host. The purified muteins retained comparable kinetics parameters in plasminogen activation and showed different degrees of resistance to plasmin depending on the nature of the mutation. Muteins with double mutations had half-lives that were extended 21-fold when assayed in a 1:1 molar ratio with plasminogen in vitro and showed better plasminogen activation activity with time in the radial caseinolysis assay. This study indicates that plasmin-mediated processing leads to the inactivation of streptokinase and is not required to convert streptokinase to its active form. Plasmin-resistant forms of streptokinase can be engineered without affecting their activity, and blockage of the N-terminal cleavage site is essential to generate engineered streptokinase with a longer in vitro functional half-life.
Intracellular MHC Class II Controls Regulatory Tolerance to Allogeneic Transplants (2010)

MHC class II (MHCII) genes have been implicated in the regulation of T lymphocyte responses. However, the mechanism of MHCII-driven regulation remains unknown. Matching for MHCII between donors and recipients of allografts favors regulatory T cell tolerance to transplants and provides a unique opportunity to study this regulation. In this study, we investigated MHCII regulation using transfer of donor MHCII genes in recipients of cardiac allografts. Transfer of MHCII IA(b) genes in the bone marrow of CBA mice (H-2(k)) prior to the grafting of IA(b+) fully allogeneic C57BL/6 (B6, H-2(b)) heart transplants resulted in donor-specific tolerance associated with long-term survival of B6, but not third-party, allografts without sustained immunosuppression. Strikingly, the majority of accepted heart transplants (>170 d) were devoid of allograft vasculopathy. Further studies indicated that intracellular IA(b) initiated the tolerogenic process, which was mediated by regulatory T cells (Tregs) that polarized antigraft responses to Th2 cytokine producers. This mechanism seems to be unique to MHCII genes, because previous MHC class I gene-based therapies failed to produce Tregs. These results demonstrate the key role of MHCII in the induction of Tregs. They also underscore a potential mechanism of specific inactivation of T cells in this model; when activated by IA(b+) grafts, IA(b)-specific Tregs repress the entire alloresponse to C57BL/6 transplants (including MHC I and minor Ags), thus mediating T cell tolerance.
Intracellular Butyryl Phosphate and Acetyl Phosphate Concentrations in Clostridium acetobutylicum and Their Implications for Solvent Formation (2005)

It has been suggested (L. H. Harris, R. P. Desai, N. E. Welker, and E. T. Papoutsakis, Biotechnol. Bioeng. 67:1-11, 2000) that butyryl phosphate (BuP) is a regulator of solventogenesis in Clostridium acetobutylicum. Here, we determined BuP and acetyl phosphate (AcP) levels in fermentations of C. acetobutylicum wild type (WT), degenerate strain M5, a butyrate kinase (buk) mutant, and a phosphotransacetylase (pta) mutant. A sensitive method was developed to measure BuP and AcP in the same sample. Compared to the WT, the buk mutant had higher levels of BuP and AcP; the BuP levels were high during the early exponential phase, and there was a peak corresponding to solvent production. Consistent with this, solvent formation was initiated significantly earlier and was much stronger in the buk mutant than in all other strains. For all strains, initiation of butanol formation corresponded to a BuP peak concentration that was more than 60 to 70 pmol/g (dry weight), and higher and sustained levels corresponded to higher butanol formation fluxes. The BuP levels never exceeded 40 to 50 pmol/g (dry weight) in strain M5, which produces no solvents. The BuP profiles were bimodal, and there was a second peak midway through solventogenesis that corresponded to carboxylic acid reutilization. AcP showed a delayed single peak during late solventogenesis corresponding to acetate reutilization. As expected, in the pta mutant the AcP levels were very low, yet this strain exhibited strong butanol production. These data suggest that BuP is a regulatory molecule that may act as a phosphodonor of transcriptional factors. DNA array-based transcriptional analysis of the buk and M5 mutants demonstrated that high BuP levels corresponded to downregulation of flagellar genes and upregulation of solvent formation and stress genes.
Electrical impedance for estimation of irritation in oral mucosa and skin. (1995)

Our aim is to establish an objective, easy-to-use technique to evaluate tissue irritation in vivo using non-invasive electrical impedance measurements. Such a technique would facilitate testing the biocompatibility of various materials, and also in quantifying skin diseases and other processes involving structural changes. It has been found that irritation of the oral mucosa not clinically or histologically discernible could be detected with a simple device based on electrical impedance techniques. Originally, the key problem was to focus the probing electrical field in order to minimize artefacts emanating from tissue layers of no interest. The device was then refined and applied to skin testing. It was found that irritation effects far below the limit of the commonly used visual readings could be detected. In this case, it is desirable to exclude from the measurement tissue layers with no diagnostic information, or at least reduce their influence. In this paper, the essential steps of the development of a multi-frequency depth selective device are reviewed.
A New Dressing Method for Free Skin Grafting in Hands (1991)

Using adhesive drapes and a disposable suction drain, the grafted area is compressed by positive pressure that is equivalent to the negative pressure of a suction drain. With this dressing method, the graft can be observed throughout the postoperative course, and can be applied with uniform and constant pressure. Thin drapes accommodate well to various shapes, so this method is uniquely qualified in free skin grafting of hands.
Recovery of the matrix operators in the similarity and congruency transformations: applications in polarimetry (1993)

Formulas are presented for the recovery of the matrix operators in arbitrary-order similarity and congruency transformations. Two independent input and output matrix pairs exactly determine the similarity-transformation matrix operator, while three independent Hermitian-matrix pairs are required for the congruency-transformation operator. The congruency transformation is the natural form for the quantum observables of a multiple-element wave function, e.g., for polarized-light transfer: the recovery of the Jones matrix for a nondepolarizing device is demonstrated, given any three linearly independent partially polarized input Stokes states. The recovery formula gives a good solution even with large added noise in the test matrices. Combined with numerical least-squares methods, the formula can give an optimized solution for measures of observation error. A more general operator, which includes the effect of isotropic depolarization, is defined, and its recovery is demonstrated also. The recovery formulas have a three-dimensional geometric interpretation in the second-order case, e.g., in the Poincaré sphere. It is pointed out that the geometric property is a purely mathematical property of quantum observables that arises without referring to spatial characteristics for the underlying wave function.
Quantitative determination of rare mRNA species by PCR and solid-phase minisequencing. (1992)

We present a new method for quantification of mRNA, in which the limitations of the current quantitative PCR methods can be overcome. A known amount of a synthetic RNA standard differing from the mRNA to be quantified by a single nucleotide is reverse-transcribed and amplified together with the mRNA template using a biotinylated primer. The biotinylated PCR product is immobilized on a streptavidin-coated solid support and denatured. The ratio between the two amplified sequences is determined by separate "mini-sequencing" reactions, in which a detection step primer annealing immediately adjacent to the site of the variable nucleotide is elongated by a single labeled dNTP complementary to the nucleotide at the variable site. The ratio between the incorporated labels accurately determines the ratio between the two sequences in the original RNA sample. We applied this method to quantify the mRNA of human aspartylglucosaminidase (AGA) in tissues and cultured cells. AGA is a lysosomal enzyme participating in the degradation of glycoproteins. A mutation in the AGA gene abolishes the enzyme activity and leads to aspartylglucosaminuria (AGU), a recessively inherited metabolic disorder. The mRNA quantification revealed that the normal and mutant genes are expressed at similar levels in kidney, liver, and cultured fibroblast, whereas the amount of AGA mRNA in normal placenta and brain is significantly higher than that found in the corresponding samples from AGU patients. The method presented here is generally applicable for PCR-based quantification of rare mRNAs and DNA as well.
Coded random access design for constrained outage (2017)

The emergence of networks of many devices in the context of cyber-physical systems motivates novel solutions for communication over random access channels. Currently deployed random access protocols attempt to avoid collisions, and target the performance of a scheduled multiple access system (a strategy known to be only suboptimal from the information-theoretic perspective). In contrast, in this paper, we allow collisions among the transmissions of different users. We consider code design for random access channels with erasures in which the number of users in each frame is unknown at the transmitters but known at the receiver, and we present a two-layer coding architecture for joint contention resolution and erasure correction. For random LDPC codes based on this scheme, the density evolution is asymptotically analyzed, which enables optimized code design for maximized throughput with constrained outage. The results demonstrate that the proposed low-complexity scheme approaches the outage capacity of the random access channel with erasures when the average number of active users is small.
Safety and immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants (2001)

Use of the pentavalent combination vaccine would greatly reduce the number of required injections during the first 2 years of life, thereby simplifying the immunization schedule, enhancing compliance and facilitating acceptance of additional injections engendered by introduction of newer vaccines.
Mechanics Modeling of Tendon-Driven Continuum Manipulators (2008)

Continuum robotic manipulators articulate due to their inherent compliance. Tendon actuation leads to compression of the manipulator, extension of the actuators, and is limited by the practical constraint that tendons cannot support compression. In light of these observations, we present a new linear model for transforming desired beam configuration to tendon displacements and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">vice</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">versa</i> . We begin from first principles in solid mechanics by analyzing the effects of geometrically nonlinear tendon loads. These loads act both distally at the termination point and proximally along the conduit contact interface. The resulting model simplifies to a linear system including only the bending and axial modes of the manipulator as well as the actuator compliance. The model is then manipulated to form a concise mapping from beam configuration-space parameters to <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</i> redundant tendon displacements via the internal loads and strains experienced by the system. We demonstrate the utility of this model by implementing an optimal feasible controller. The controller regulates axial strain to a constant value while guaranteeing positive tendon forces and minimizing their magnitudes over a range of articulations. The mechanics-based model from this study provides insight as well as performance gains for this increasingly ubiquitous class of manipulators.
Xylitol production by Enterobacter liquefaciens. (1976)

An extract of cells of D-xylose-utilizing Enterobacter liquefaciens No. 553 grown in a D-xylose medium showed NADPH-dependent D-xylose reductase, glucose 6-phosphate dehydrogenase, phosphogluconate dehydrogenase and isocitrate dehydrogenase activities. D-Xylose isomerase, D-xylulokinase, transketolase and phosphoglucose isomerase activities were also found in the cell-free extract. These enzymes were fractionated by Sephadex G-100 gel filtration and DEAE-cellulose column chromatography, and some of their properties were examined. The reduction of D-xylose to xylitol was confirmed by the coupling of the fractionated D-xylose reductase and the glucose 6-phosphate dehydrogenase, phosphogluconate dehydrogenase or isocitrate dehydrogenase with NADP as a cofactor. The presence of NADPH in the cells accelerated the conversion of D-xylose into xylitol and repressed the isomerization of n-xylose into D-xylulose. The level of NAD-dependent xylitol dehydrogenase in the cells and the rate of reverse reaction by the D-xylose reductase dropped under the conditions favoring the production of xylitol.
P3‐400: Biotin deficiency and abnormal pantothenic acid levels in dementia (2008)

Biotin and pantothenic acid deficiences are thought to be rare conditions. Elevated levels of pantothenic acid, a water-soluble vitamin, have not been reported in the medical literature. These vitamins are essential for energy metabolism and acetylcholine production. More than 50 patients in our memory clinic have been identified with biotin deficiency. Half of these patients have elevated pantothenic acid levels and a third have a pantothenic acid deficiency. Changes in the globus pallidus interna (GPi) on magnetic resonance imaging (MRI) have been identified which appear to correlate with biotin deficiency and dementia. Serum levels of biotin and pantothenic acid were obtained on 54 patients being evaluated in a community-based memory clinic when they presented with a dementia and T2-weighted MRI images revealed hypointensity in the GPi with or without an area of central hyperintensity. Hippocampal atrophy was estimated by the author using coronal MRI images at the level of the mammillary bodies. Abnormal serum biotin levels were identified in 96.3% of patients with dementia and hypointensity of the GPi on T2-weighted MRI; 50 patients (92.6%) had a biotin deficiency (<200 pg/ml) and 74% had biotin levels <100 pg/ml. Pantothenic acid levels were normal in ten patients (normal range 200–1800 ng/ml), elevated in 50% of patients (range 2081–28,597 ng/ml) and low in 31.5% of patients. Hippocampal atrophy was absent or mild in 45/54 cases (83%). An area of central hyperintensity within the GPi hypointensity is seen in 39/54 cases (72%). Biotin deficiency and abnormal levels of pantothenic acid are extremely common in this cohort of patients with dementia and hypointensity of the GPi on T2-weighted MR images. Three quarters of these patients have biotin levels below the sensitivity limit of the test (<100 pg/ml) and a quarter have pantothenic acid levels >3 times the upper limit of normal, a finding not previously reported in the medical literature. Biotin and pantothenic acid are carried across cell membranes by the sodium-dependent multivitamin transporter (SMVT). These findings implicate dysregulation of the SMVT in a dementia exhibiting changes within the GPi and without the hippocampal atrophy commonly seen in Alzheimer's disease.
Cell-Free Protein Synthesis for Functional and Structural Studies (2013)

Recent advances in cell-free protein expression systems have made them reliable and practical for functional and structural studies of a wide variety of proteins. In particular, wheat germ cell-free translation can consistently produce target proteins in microgram quantities from relatively inexpensive, small-scale reactions. Here we describe our small-scale protein expression method for rapidly producing proteins for functional assay and techniques for determining if the target is suitable for scale-up to amounts potentially needed for structure determination. The cell-free system is versatile and can be easily customized with the inclusion of additives. We describe simple modifications used for producing membrane proteins.
The application of monoclonal antibodies to the characterization and diagnosis of lymphoid neoplasms: a review of recent studies. (1983)

Twenty-three T-cell neoplasms were divided, according to their reactivity with the OKT monoclonal antibodies as follows: Fourteen neoplasms of diverse histopathology expressed the OKT3+ OKT4+ phenotype, commonly associated with the helper T-cell subset; seven histologically similar lymphoblastic neoplasms expressed diverse phenotypes consistent with various stages of intrathymic differentiation and two neoplasms expressed the uncommon OKT3+ OKT10+ phenotype. Thus, T-cell neoplasms are divisible into phenotypes that correspond to normal stages of T-cell differentiation and functionally distinct T-cell subsets. Benign and malignant lymphoid cells were investigated in cell suspension and in cryostat tissue sections for their reactivity with OKB1, OKB2, OKB4, and OKB7, monoclonal antibodies known to detect distinctive B lymphocyte antigens. Fetal liver pre-B cells, cases of pre-B acute lymphoblastic leukemia, and common-type acute lymphoblastic leukemia were OKB2+ but unreactive with the other OKB antibodies. All mature lymphoid tissue B cells and 47/47 surface immunoglobulin (SIg)-positive B-cell neoplasms were OKB2+. Interfollicular, follicular center, and many, but not all, mantle zone B cells were OKB1+ OKB7+. Follicular center B cells were OKB4+ but mantle zone and interfollicular B cells were OKB4-. 45/47 SIg+ B-cell neoplasms were OKB1+ OKB4+. 45/46 SIg+ B-cell neoplasms were OKB7+. Benign and myeloma plasma cells were OKB-. T-cell neoplasms were OKB2- OKB4- but were occassionally OKB1+ and OKB7+. The OKB antibodies appear to detect distinctive antigens that may be expressed at different stages of B-cell differentiation.
Signal transduction by immunoglobulin Fc receptors (1998)

Receptors for the Fc portion of immunoglobulin molecules (FcR) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense. Cross-linking of FcR by immune complexes leads to functions such as phagocytosis, cell cytotoxicity, production and secretion of inflammatory mediators, and modulation of the immune response. Molecular characterization of FcRs indicates the existence of several types of these receptors, which seem to be redundant in their cell distribution and function. There is a great deal of interest in understanding how these various receptors signal the cell to respond in different ways during inflammation and the immune response. Previous studies indicate that FcR signaling shares elements with the T and B cell antigen receptors. Signaling is initiated in all of them by activation of tyrosine kinases of the Src and ZAP-70 families. Subsequent events, which vary depending on the cell type and receptor involved, include activation of other enzymes such as phospholipase Cgamma1, phosphatidylinositol-3-kinase, and mitogen-activated protein kinase. Several recent lines of research, including studies of phagocytosis by FcR-transfected cells, antibody-dependent cytotoxicity by natural killer cells, mast cell degranulation, and FcR-deficient mice, have given us new insights on the signal transduction pathways activated by FcRs. This review describes the advances in these areas and presents a general model for FcR-mediated signaling.