gebhart/patrepeval huggingface dataset:
Nutritional Management of Phenylketonuria (2010)

Phenylketonuria (PKU) is caused by deficient activity of the enzyme phenylalanine hydroxylase, needed to convert the essential amino acid (AA) phenylalanine (phe) to tyrosine. In order to prevent neurological damage, lifelong adherence to a low-phe diet that is restricted in natural foods and requires ingestion of a phe-free AA formula to meet protein needs is required. The goal of nutritional management for those with PKU is to maintain plasma phe concentrations that support optimal growth, development, and mental functioning while providing a nutritionally complete diet. This paper reviews developing a lifelong dietary prescription for those with PKU, outcomes of nutritional management, compliance with the low-phe diet across the life cycle, and new options for nutritional management. An individualized dietary prescription is needed to meet nutrient requirements, and the adequacy of phe intake is monitored with assessment of blood phe levels. Elevated phe concentrations may occur due to illness, excessive or inadequate phe intake, or inadequate intake of AA formula. Although normal growth and development occurs with adherence to the low-phe diet, it is important to monitor vitamin, mineral and essential fatty acid status, especially in those who do not consume sufficient AA formula. Given the growing population of adults with PKU, further research is needed to understand the risks for developing osteoporosis and cardiovascular disease. There are promising new options to liberalize the diet and improve metabolic control such as tetrahydrobiopterin therapy or supplementation with large neutral AAs. Moreover, foods made with glycomacropeptide, an intact protein that contains minimal phe, improves the PKU diet by offering a palatable alternative to AA formula. In summary, continued efforts are needed to overcome the biggest challenge to living with PKU - lifelong adherence to the low-phe diet.
Kinetics of endocytosis and recycling of the GPI-anchored variant surface glycoprotein inTrypanosoma brucei (2004)

The dense coat of glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG) covering parasitic African trypanosomes is essential for survival in mammalian hosts. VSG is internalised and recycled exclusively via a specialised part of the plasma membrane, the flagellar pocket. Direct measurement of the kinetics of VSG endocytosis and recycling shows that the VSG cell-surface pool is turned over within 12 minutes. Correspondingly, the turnover of the intracellular pool (9+/-4% of total VSG) requires only 1 minute, and this is an exceptionally high rate considering that endocytosis and exocytosis are limited to only 5% of the cell surface area. Kinetic 3D co-localisation analysis using biotinylated VSG and a panel of compartmental markers provides consistent evidence for the itinerary of VSG through the cell: VSG is endocytosed in large clathrin-coated vesicles, which bud from the flagellar pocket membrane at a rate of 6-7 vesicles per second, and is then delivered to RAB5-positive early endosomes. From there, VSG is recycled to RAB11-positive recycling endosomes at two stages, either directly or via RAB7-positive, late endosomes. Small clathrin-coated vesicles carrying fluid-phase cargo and being depleted of VSG bud from early and recycling endosomes. These vesicles are postulated to deliver their content to late endosomes and/or the lysosome. The recycling endosomes give rise to RAB11-positive exocytic carriers that fuse with the flagellar pocket and thereby return VSG to the cell surface. VSG recycling provides an interesting model for studies on the cellular trafficking and sorting of GPI-anchored proteins.
Factors responsible for the introduction and spread of Campylobacter jejuni infection in commercial poultry production. (1990)

Campylobacter jejuni and related thermophilic campylobacters were not found in a hatchery or in chicks aged less than seven days. However, an increasing proportion of chicks aged two weeks and older shed campylobacters in their droppings. It was shown that a likely source of C jejuni for young chicks was the environment in the immediate vicinity of the rearing houses, and that infection could readily be introduced on the footwear and clothing of farm staff. Thermophilic campylobacters were found in the air, litter and drinking water containers in the rearing and finishing houses.
Phenotypic classification of human CD4+ T cell subsets and their differentiation (2008)

CD4(+) T cells have T(h) cell function and include two major functional subsets, T(h)1 and T(h)2. However, there are a restricted number of studies concerning phenotypic classification of human CD4(+) T cells. Here by using seven- and eight-color flow cytometric analysis, we investigated the function of the subsets classified by four markers, CD27, CD28, CD45RA and CCR7. Five major subsets were identified by using these markers. These subsets showed different patterns of cytokine production after they were stimulated with phorbol myristate acetate and ionomycin. The analyses of cytokine production suggested that CCR7(+)CD45RA(+)CD27(+)CD28(+), CCR7(+)CD45RA(-)CD27(+)CD28(+) and CCR7(-)CD45RA(-)CD27(+)CD28(+) subsets were naive, central memory and effector memory T cells, respectively, whereas CCR7(-)CD45RA(-)CD27(-)CD28(+) and CCR7(-)CD45RA(-)CD27(-)CD28(-) subsets included T(h)1 and T(h)2 cells. The analysis of cytokine production by these subsets stimulated with anti-CD3 and anti-CD28 mAbs or with human cytomegalovirus antigens showed that IFN-gamma production was significantly higher in the CCR7(-)CD45RA(-)CD27(-)CD28(-) subset than in other subsets and that both CCR7(-)CD45RA(-)CD27(-)CD28(+) and CCR7(-)CD45RA(-)CD27(-)CD28(-) subsets produced a higher level of IL-4 than did other subsets. Our analyses demonstrated that the CCR7(-)CD45RA(-)CD27(-)CD28(-) subset predominantly included T(h)1 effector cells and that CCR7(-)CD45RA(-)CD27(-)CD28(+) subsets included T(h)1 and T(h)2 effector memory/effector cells as well as unclassified cells. The analysis of classification by using these four markers also suggested the differentiation pathway of human CD4(+) T cells.
Influence of albumin on itraconazole and ketoconazole antifungal activity: results of a dynamic in vitro study (1991)

The relevance of intense protein binding to the antifungal activity of azole compounds is still a matter of debate. The influence of albumin on the antimicrobial activity of ketoconazole and itraconazole, which exhibit very strong plasma protein binding (99 and 99.8%), was evaluated in vitro. Candida albicans was exposed to continuously changing azole concentrations corresponding to drug levels in serum following an oral dose of 200 mg. Total as well as free drug levels in serum were simulated. The incubation medium was free of proteins or contained 4% human serum albumin. Itraconazole levels reflecting free drug concentrations in humans did not reduce the growth rate of C. albicans, as compared with controls (difference in the log CFU per milliliter at 12 h, 0.03 +/- 0.09), whereas total drug levels were as active in the presence of 4% albumin (mean difference, -0.61) as in its absence (-0.75). The same was true for ketoconazole, except that free drug levels were also active (-1.21 versus -1.39 for total drug levels). This result was due to the higher ketoconazole levels in humans. Thus, in terms of routine susceptibility testing, in vitro total drug levels can be considered relevant.
On Memory Saved by Randomization (1971)

It is known that deterministic automata are generally not optimal in the problem of learning with finite memory. It is natural to ask how much memory is saved by randomization. In this note it is shown that the memory saving is arbitrarily large in the sense that for any memory size $m < \infty$, and $\delta > 0$, there exist problems such that all $m$-state deterministic algorithms have probability of error $P(e) \geqq \frac{1}{2} - \delta$, while the optimal two-state randomized algorithm has $P(e) \leqq \delta$.
Mono-sized single-wall carbon nanotubes formed in channels of AlPO4-5 single crystal (1998)

An alternative approach to the synthesis of mono-sized and parallel-aligned single-wall carbon nanotubes (SWCNs) is reported. The SWCNs are formed in 0.73 nm sized channels of microporous aluminophosphate crystallites by pyrolysis of tripropylamine molecules in the channels. They are characterized through transmission electron microscopy, polarized Raman scattering, and electrical transport measurements. Our results would open a door to further detailed studies on the intrinsic properties of carbon nanotubes now in progress.
Nucleic acid delivery using poly(ethylenimine)-based polymers for programmed death-ligand 1 (PD-L1) knockdown in ovarian cancer to enhance immunotherapy (2015)

Ovarian cancer remains the most lethal gynaecological cancer mainly due to the lack of reliable biomarkers and eventual development of chemo-resistance. This emphasizes the need for better therapies. Ovarian cancer is considered as an immunogenic tumour and adoptive immunotherapy is a promising treatment strategy. However, co-inhibitory molecules such as programmed death-ligand 1 (PD-L1), highly expressed on ovarian cancer cells interacts with its receptor, programmed death-1 (PD-1), expressed on T cells, causing immunosuppression. The aim of this Ph.D. was to 1) develop more efficient and targeted gene delivery agents by functionalizing poly(ethylenimine) (PEI) with various hydrophobic groups and folic acid (FA) targeting ligand, 2) deliver PD-L1 small interfering RNA (siRNA) or short hairpin RNA (shRNA) into ovarian cancer cells to block PD-1/PD-L1 interactions and 3) to study how T cell function and anti-tumour activity are affected as a consequence of PD-L1 knockdown. 4) In addition, detection of soluble PD-L1 (sPD-L1), using an enzyme linked immunosorbent assay (ELISA) and an Acoustic Membrane MicroParticle (AMMP) technology was also studied for its potential use as a biomarker for ovarian cancer diagnosis. When PEI was functionalized with various hydrophobic functional groups (ethyl, octyl, deodectyl, benzl, phenyl urea) using the established methyl-carboxytrimethylene carbonate (MTC) platform, cytotoxicity was greatly reduced (for PEI, Mn=10 kDa) and gene transfection efficiency was substantially enhanced (Teo et al., 2013, Yang et al., 2013). Hydrophobic modification, however, did not improve siRNA delivery and PEI polymers functionalized with FA targeting groups (FA, poly(ethylene glycol) (PEG), PEG-FA), were investigated for PD-L1 delivery. FA-functionalized PEI displayed a higher specificity of uptake into ovarian cancer cells. PD-L1 knockdown in ovarian cancer cells using FA-functionalized PEI/PD-L1 siRNA polyplexes rendered tumour cells more susceptible to killing by chimeric antigen receptor (CAR) expressing T cells (Teo et al., 2015). In addition, an in-house ELISA, but not the AMMP platform, successfully detected sPD-L1 in patient plasma which differentiated patients with benign or malignant disease. In conclusion, PD-L1 has tremendous potential as a therapeutic and diagnostic target for ovarian cancer. Furthermore, modified PEI gene delivery agents has been shown to be an effective therapeutic tool in ovarian cancer and its use may be extended to a wide range of diseases which arise due to errant genes.
Structural and Catalytic Similarities between Nucleotide Pyrophosphatases/Phosphodiesterases and Alkaline Phosphatases (2001)

Nucleotide pyrophosphatases/phosphodiesterases (NPPs) generate nucleoside 5'-monophosphates from a variety of nucleotides and their derivatives. Here we show by data base analysis that these enzymes are conserved from eubacteria to higher eukaryotes. We also provide evidence for the existence of two additional members of the mammalian family of ecto-NPPs. Homology searches and alignment-assisted mutagenesis revealed that the catalytic core of NPPs assumes a fold similar to that of a superfamily of phospho-/sulfo-coordinating metalloenzymes comprising alkaline phosphatases, phosphoglycerate mutases, and arysulfatases. Mutation of mouse NPP1 in some of its predicted metal-coordinating residues (D358N or H362Q) or in the catalytic site threonine (T238S) resulted in an enzyme that could still form the nucleotidylated catalytic intermediate but was hampered in the second step of catalysis. We also obtained data indicating that the ability of some mammalian NPPs to auto(de)phosphorylate is due to an intrinsic phosphatase activity, whereby the enzyme phosphorylated on Thr-238 represents the covalent intermediate of the phosphatase reaction. The results of site-directed mutagenesis suggested that the nucleotide pyrophosphatase/phosphodiesterase and the phosphatase activities of NPPs are mediated by a single catalytic site.
Antigen-Specific Primary Activation of CD8+ T Cells Within the Liver (2001)

It is generally accepted that naive T cells recirculate via the blood and lymph, but do not enter nonlymphoid tissues without prior activation and differentiation. In this study, we demonstrate that the liver is an exception to this rule. Naive Des-TCR transgenic CD8(+) T cells specific for H-2K(b) were selectively retained in the liver within a few minutes of adoptive transfer into transgenic Met-K(b) mice expressing H-2K(b) in the liver. Activated CD8(+) cells were found in the liver, but not the blood, as soon as 2 h after transfer and underwent cell division and started to recirculate within 24 h of transfer. In contrast, CD8(+) cells activated in the lymph nodes remained sequestered at that site for 2 days before entering the blood. Our results therefore suggest that, in addition to its previously described role as a non Ag-specific activated T cell graveyard, the liver is involved in Ag-specific activation of naive recirculating CD8(+) T cells. This particular property of the liver, combined with the previously demonstrated ability of hepatocytes to induce tolerance by means of premature CD8(+) T cell death, may be a major mechanism contributing to the acceptance of liver allografts and the chronicity of viral hepatitis.
Application of AMR Based on Powerline Communication in Outage Management System (2010)

At present power company challenge is how to quickly and effectually implement outage management, the upgrade of both metering technology and communication system makes the development of automated meter reading (AMR) systems possible. Signals from automated meters can provide extra information for outage detection and decision processing as well as restoration phases of outage management. In this paper an algorithm efficiently using available information from distribution network supervisory control and data acquisition (SCADA) and AMR systems based on power line communication (PLC) to locate outage sources is presented. Using the polling characteristic of AMR based on PLC can identify the scope of outage, by polling these meters adjacent to the meter with a trouble call, the customers affected by outage can be identified; by upstream tracing the connectivity of trouble calls to find a common point, outage locations can be identified. Using AMR in outage management system (OMS) can bring enormous profits to power industry, it reduces electric utility's cost, shortens outage duration and improves consumer's satisfaction.
Comparison of the structures of the quinone-binding sites in beef heart mitochondria. (1993)

The ubiquinone pool in mitochondrial membranes serves as an electron carrier between both NADH-coenzyme Q oxidoreductase (Complex I) and succinate-coenzyme Q oxidoreductase (Complex II) and ubiquinol-cytochrome-c oxidoreductase (Complex III). It has been reported (Saitoh, I., Miyoshi, H., Shimizu, R., and Iwamura, H. (1992) Eur. J. Biochem. 209, 73-79) that 2-alkyl-4,6-dinitrophenols compete with exogenous coenzyme Q (Q) to inhibit electron transport through cytochromes b and c1 in mammalian mitochondria as well as in photosystem II. We have probed the similarities and differences in the reaction sites of exogenous Q in all three segments of the respiratory chain using selected 2-alkyl-4,6-dinitrophenols. The inhibition of Q analog reduction by the dinitrophenol derivatives was competitive for Complex I and noncompetitive for Complex II. The inhibition of Complex III was competitive with the pentyl analog, but was uncompetitive with the decyl analog, which may be due to different interactions of the two quinol analogs with Complex III. The degree of inhibition by several of these compounds was comparable for Complexes I and III, but Complex II was inhibited to a much smaller extent. The inhibitory potency of these compounds for Complexes I and III was increased by branching and by lengthening the carbon chain at the 2-position equivalent to the isoprenoid side chain of ubiquinone. Hydrophobic substituents increased the inhibition of Complex II. Replacement of the phenolic OH group by a chlorine atom decreased the maximum inhibition of Complex III, but increased that of Complex I. These data suggest that the structures of the exogenous Q-binding sites in Complexes I and III may be similar, but not identical, and that they are different from that in Complex II.
Genotyping of Francisella tularensis Strains by Pulsed-Field Gel Electrophoresis, Amplified Fragment Length Polymorphism Fingerprinting, and 16S rRNA Gene Sequencing (2002)

We evaluated three molecular methods for identification of Francisella strains: pulsed-field gel electrophoresis (PFGE), amplified fragment length polymorphism (AFLP) analysis, and 16S rRNA gene sequencing. The analysis was performed with 54 Francisella tularensis subsp. holarctica, 5 F. tularensis subsp. tularensis, 2 F. tularensis subsp. novicida, and 1 F. philomiragia strains. On the basis of the combination of results obtained by PFGE with the restriction enzymes XhoI and BamHI, PFGE revealed seven pulsotypes, which allowed us to discriminate the strains to the subspecies level and which even allowed us to discriminate among some isolates of F. tularensis subsp. holarctica. The AFLP analysis technique produced some degree of discrimination among F. tularensis subsp. holarctica strains (one primary cluster with three major subclusters and minor variations within subclusters) when EcoRI-C and MseI-A, EcoRI-T and MseI-T, EcoRI-A and MseI-C, and EcoRI-0 and MseI-CA were used as primers. The degree of similarity among the strains was about 94%. The percent similarities of the AFLP profiles of this subspecies compared to those of F. tularensis subsp. tularensis, F. tularensis subsp. novicida, and F. philomiragia were less than 90%, about 72%, and less than 24%, respectively, thus permitting easy differentiation of this subspecies. 16S rRNA gene sequencing revealed 100% similarity for all F. tularensis subsp. holarctica isolates compared in this study. These results suggest that although limited genetic heterogeneity among F. tularensis subsp. holarctica isolates was observed, PFGE and AFLP analysis appear to be promising tools for the diagnosis of infections caused by different subspecies of F. tularensis and suitable techniques for the differentiation of individual strains.
Adhesion of Vi Antigen and Toxicity in Typhoid Vaccines Inactivated by Acetone or by Heat and Phenol (1974)

The method of preparation of typhoid vaccine influenced the adhesion of Vi antigen to the bacterial cell and the serologic and protective activity of the vaccine. The acetone-inactivated vaccine 6A and vaccine L, inactivated by heat and phenol, possessed approximately equal amounts of Vi antigen, extractable in 0.85% NaCl; the antigens had equal protective activity for mice. After extraction, bacteria in vaccine 6A retained a significant amount of Vi antigen, which was demonstrable by serologic and immunologic tests, whereas the bacteria in vaccine L retained practically no Vi antigen. Vaccine 6A decreased in potency only 2.5-fold, and vaccine L decreased ninefold. Heating at 56 C during preparation of vaccine L did not affect the non-Vi protective factor(s) or the protective activity of extracted Vi antigen. The superior potency of vaccine 6A was attributed to fixation of the Vi antigen to the bacteria by acetone. Treatment of bacterial cells with acetone slightly reduced endotoxicity for mice and mouse lymphoid cells, but the difference between vaccine 6A and vaccine L was not significant. The results reflect the variable differences in the reactions of man to vaccine K and vaccine L observed in the field trials.
Characterization and evolutionary history of an archaeal kinase involved in selenocysteinyl-tRNA formation (2008)

Selenocysteine (Sec)-decoding archaea and eukaryotes employ a unique route of Sec-tRNA(Sec) synthesis in which O-phosphoseryl-tRNA(Sec) kinase (PSTK) phosphorylates Ser-tRNA(Sec) to produce the O-phosphoseryl-tRNA(Sec) (Sep-tRNA(Sec)) substrate that Sep-tRNA:Sec-tRNA synthase (SepSecS) converts to Sec-tRNA(Sec). This study presents a biochemical characterization of Methanocaldococcus jannaschii PSTK, including kinetics of Sep-tRNA(Sec) formation (K(m) for Ser-tRNA(Sec) of 40 nM and ATP of 2.6 mM). PSTK binds both Ser-tRNA(Sec) and tRNA(Sec) with high affinity (K(d) values of 53 nM and 39 nM, respectively). The ATPase activity of PSTK may be activated via an induced fit mechanism in which binding of tRNA(Sec) specifically stimulates hydrolysis. Albeit with lower activity than ATP, PSTK utilizes GTP, CTP, UTP and dATP as phosphate-donors. Homology with related kinases allowed prediction of the ATPase active site, comprised of phosphate-binding loop (P-loop), Walker B and RxxxR motifs. Gly14, Lys17, Ser18, Asp41, Arg116 and Arg120 mutations resulted in enzymes with decreased activity highlighting the importance of these conserved motifs in PSTK catalysis both in vivo and in vitro. Phylogenetic analysis of PSTK in the context of its 'DxTN' kinase family shows that PSTK co-evolved precisely with SepSecS and indicates the presence of a previously unidentified PSTK in Plasmodium species.
Osteoporosis: a bone morphogenetic protein auto-immune disorder. (1985)

Simultaneous reduction in the bone formation phase, and a normal or accelerated bone resorption phase of the bone remodelling process occurs in patients with severe osteoporosis having normal calcium or mineral intake, endocrine function, and exercise patterns. A large body of research suggests that the resorption phase is under the control of the immune system, cell mediated, and involves interaction of macrophages and T-lymphocytes. Much less is known about the bone formation phase. The present hypothesis is based upon speculation on the immunosuppressive effects of B-cell-synthesized humoral antibody (anti-BMP) against bone morphogenetic protein, subsequently reducing osteoprogenitor cell differentiation and causing either gradual or precipitous decline in bone mass. The hypothesis assumes that approximately 74% of white Caucasian women of postmenopausal age, and nearly all of the black population in the USA who do not develop osteoporosis, maintain a low anti-BMP titre. The hypothesis emphasizes a recorded (albeit low) incidence of osteoporosis in children, postpartum women, young men, exogenous adrenal hypercorticoidism, various endocrinopathies who warrant investigation for auto-immune disease. Based upon a high anti-BMP titre, and a low BMP anti-BMP ratio in 10 patients with severe osteoporosis, the hypothesis proposes investigation of an auto-immune disorder in the 26% of the female population who become disabled by severe osteoporosis.