gebhart/patrepeval huggingface dataset:
Solve the IRP problem with an improved discrete differential evolution algorithm (2019)

The inventory -routing problem is a NP hard problem. It is difficult to find the optimal solution in polynomial time. Many scholars have studied it in many years. This paper analyses the inventory-routing optimisation problem, and comprehensive differential evolution algorithm is good performance in solving combinatorial optimisation problems. The differential evolution algorithm was improved to make it be suitable for solving discrete combination optimisation problems. In order to improve the performance of the differential evolution algorithm to solve the inventory routing problem, this paper puts forward dynamic adjustment of mutation factor and crossover factor of the differential evolution. It is proved by numerical experiments that the proposed algorithm has certain performance advantages, and it also proves that the improved algorithm can improve the performance of the algorithm by dynamic adjustment of the mutation factor and crossover factor.
SHPS-1 promotes the survival of circulating erythrocytes through inhibition of phagocytosis by splenic macrophages (2005)

The lifespan of circulating red blood cells (RBCs) produced in bone marrow is determined by their elimination through phagocytosis by splenic macrophages. The mechanism by which RBC elimination is regulated has remained unclear, however. The surface glycoprotein SHPS-1, a member of the immunoglobulin superfamily, is abundant in macrophages. We have now examined the regulation of RBC turnover with the use of mice that express a mutant form of SHPS-1 lacking most of its cytoplasmic region. The mutant mice manifested mild anemia as well as splenomegaly characterized by expansion of the red pulp. The numbers of erythroid precursor cells in the spleen and of circulating reticulocytes were also increased in the mutant mice. In contrast, the half-life of circulating RBCs was reduced in these animals, and the rate of clearance of injected opsonized RBCs from the peripheral circulation was increased in association with their incorporation into splenic macrophages. Phagocytosis of opsonized RBCs by splenic macrophages from mutant mice in vitro was also increased compared with that observed with wild-type macrophages. These results suggest that SHPS-1 negatively regulates the phagocytosis of RBCs by splenic macrophages, thereby determining both the lifespan of individual RBCs and the number of circulating erythrocytes.
Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis (2001)

The mechanisms associated with the immunostimulatory activity of vaccine adjuvants are still poorly understood. We have undertaken a study to determine whether antigen-presenting cell trafficking is modified by administration of the submicron emulsion adjuvant MF59. We investigated the fate of inflammatory macrophages after intramuscular injection of the antigen herpes simplex virus gD2 with fluorescence-labeled MF59. A homogeneous population of macrophages infiltrated the muscle, internalized adjuvant and expressed markers characteristic of mature macrophages over a 48-h period. Macrophage influx to the injection site was reduced by 70% in mice deficient for the chemokine receptor 2 (CCR2). Two distinct cell populations were shown to contain fluorescence-labeled MF59 in the draining lymph node at 48 h post injection. The first population had a round morphology, exhibited bright fluorescence, was located in the subcapsular sinus, and was apoptotic. The second population had a dendritic morphology, was weakly fluorescent, and was located in the T cell area where adjuvant-containing apoptotic bodies identified by TUNEL labeling were present. We propose that lymph node-resident dendritic cells can acquire antigen and MF59 after intramuscular immunization by uptake of the apoptotic macrophages.
Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2 (2006)

More than 21 million prescriptions for warfarin are written yearly in the U.S. Despite its importance, warfarin's target, vitamin K epoxide reductase (VKOR), has resisted purification since its identification in 1972. Here, we report its purification and reconstitution. HPC4, a calcium-specific antibody that recognizes a 12-aa tag, was used to purify and identify VKOR. Partial reconstitution is achieved on the column by washing with 0.4% dioleoylphosphatidylcholine/0.4% deoxycholate. Activity is completely recovered by dialysis against a buffer containing a reducing agent but lacking dioleoylphosphatidylcholine/deoxycholate. Removal of detergent from the eluted proteins apparently facilitates liposome formation. Purified recombinant VKOR with tag is approximately 21 kDa, as expected; fully active; and > 93% pure. The concentration of warfarin for 50% inhibition is the same for purified protein and microsomes. It has been reported that VKOR is a multisubunit enzyme. Our results, however, suggest that a single peptide can accomplish both the conversion of vitamin K epoxide to vitamin K and vitamin K to reduced vitamin K. This purification will allow further characterization of VKOR in relation to other components of the vitamin K cycle and should facilitate its structural determination.
Micelle formation of poly(acrylic acid)-block-poly(methyl methacrylate) block copolymers in mixtures of water with organic solvents (1999)

The micelle formation of poly(acrylic acid)-block-poly(methyl methacrylate) (AA-MMA) block copolymers in mixtures of water with organic solvents was investigated by non-radiative energy transfer (NRET). In the case of block copolymers with 70 hydrophobic MMA units, which form strongly aggregated micelles in pure water, the addition of a non-selective organic solvent (methanol or 1,4-dioxane) induces a micelle-unimer transition within a relatively small range of solvent composition without significantly increasing the rate of chain exchange between micelles close to this transition region. The addition of 2 vol.-% dimethyl adipate (a solvent with chemical similarity to the PMMA block and only limited solubility in water) does not speed up the chain exchange in this system either. In contrast, this solvent promotes the aggregation of smaller block copolymers (20 or 40 MMA units) which are mainly present as single chains in pure water. In the case of the block copolymer with 40 MMA units the so formed micelles show a very slow chain exchange extending over many days. These observations prompt us to assume that the rate of the micelle-unimer exchange equilibrium is not kinetically hindered (i. e., determined by the Tg of the core material of the micelle) but controlled by a strong thermodynamic preference for the aggregated state.
Zika Virus, French Polynesia, South Pacific, 2013 (2014)

To the Editor: Isolated in 1947 from a rhesus monkey in Zika forest, Uganda, Zika virus (ZIKV) is a mosquito-borne flavivirus (1). For half a century, ZIKV was described only as causing sporadic human infections in Africa and Asia, which was mostly confirmed by serologic methods (2). In 2007, the first ZIKV outbreak reported outside Africa and Asia was retrospectively documented from biological samples of patients on Yap Island, Federated States of Micronesia, North Pacific, who had received an incorrect diagnosis of dengue virus (DENV) (3,4). We report here the early investigations that led to identification of ZIKV as the causative agent of an outbreak that started in October 2013 in French Polynesia.
Identification and Molecular Cloning of P75/Airm1, a Novel Member of the Sialoadhesin Family That Functions as an Inhibitory Receptor in Human Natural Killer Cells (1999)

In this study, by the generation of a specific monoclonal antibody, we identified p75/AIRM1 (for adhesion inhibitory receptor molecule 1), a novel inhibitory receptor that is mostly confined to human natural killer cells. p75/AIRM1 is a 75-kD glycoprotein that, upon sodium pervanadate treatment, becomes tyrosine phosphorylated and associates to src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-1. The p75/AIRM1 gene is located on human chromosome 19 and encodes a novel member of the sialoadhesin family characterized by three immunoglobulin-like extracellular domains (one NH(2)-terminal V-type and two C2-type) and a classical immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic portion. The highest amino acid sequence similarity has been found with the myeloid-specific CD33 molecule and the placental CD33L1 protein. Similar to other sialoadhesin molecules, p75/AIRM1 appears to mediate sialic acid-dependent ligand recognition.
Robotically assisted spine needle placement: program plan and cadaver study (2002)

Gives an overview of our program plan in robotically assisted spine procedures and details an initial cadaver study. Low back pain is a common medical problem, and minimally invasive procedures such as nerve blocks are rapidly growing in popularity as a potential method of treatment. To assist the physician in needle placement during these procedures, we have investigated using a needle-driver robot developed at the Johns Hopkins Urology Robotics Laboratory. Robotic systems such as these have great potential as physician-assisting devices for improving the precision of needle placement and enabling the development of the next generation of precision guidance systems for interventional techniques.
Advances in the Signal Transduction of Ceramide and Related Sphingolipids (1999)

Recently, the sphingolipid metabolites ceramide, sphingosine, ceramide 1-P, and sphingosine 1-P have been implicated as second messengers involved in many different cellular functions. Publications on this topic are appearing at a rapidly increasing rate and new developments in this field are also appearing rapidly. It is thus important to summarize the results obtained from many different laboratories and from different fields of research to obtain a clearer picture of the importance of sphingolipid metabolites. This article reviews the studies from the last few years and includes the effects of a variety of extracellular agents on sphingolipid signal transduction pathways in different tissues and cells and on the mechanisms of regulation. Sphingomyelin exists in a number of functionally distinct pools and is composed of distinct molecular species. Sphingomyelin metabolites may be formed by many different pathways. For example, the generation of ceramide from sphingomyelin can be catalyzed by at least five different sphingomyelinases. A large variety of stimuli can induce the generation of ceramide, leading to activation or inhibition of various cellular events such as proliferation, differentiation, apoptosis, and inflammation. The effect of ceramide on these physiological processes is due to its many different downstream targets. It can activate ceramide-activated protein kinases and ceramide-activated protein phosphatases. It also activates or inhibits PKCs, PLD, PLA2, PC-PLC, nitric oxide synthase, and the ERK and SAPK/JNK signaling cascades. Ceramide activates or inhibits transcription factors, modulates calcium homeostasis and interacts with the retinoblastoma protein to regulate cell cycle progression. Most of the work in this field has involved the study of ceramide effects, but the roles of the other three sphingomyelin metabolites is now attracting much attention. The complex interactions between signaling components and ceramide and the controls regulating these interactions are now being identified and are presented in this review.
Identification by PCR of Helicobacter pylori in subgingival plaque of adult periodontitis patients (1999)

The PCR was used to detect the presence of Helicobacter pylori in subgingival plaque samples from patients with adult periodontitis. Primers based upon the 16S ribosomal RNA (rRNA) gene sequence of H. pylori were used in a single round of PCR to amplify a 295-bp DNA fragment and the identity of the amplified products was confirmed by Southern blot hybridisation to a digoxigenin-labelled H. pylori probe. Further confirmation of product identity was obtained by DNA sequencing of a proportion of the amplified products. The assay was demonstrated to be specific for H. pylori with a lower limit of detection of 100 fg of bacterial genomic DNA. In all, 73 samples from 29 patients were analysed, of which 24 (33%) were H. pylori-positive by PCR; the proportion of patients carrying H. pylori in at least one sampled site was 38% (11 of 29). This is the first study to demonstrate the presence of H. pylori in the subgingival plaque of patients with adult periodontitis and indicates that, in this patient group at least, subgingival plaque may be a reservoir for H. pylori infection.
Confocal microscopy of colloids (2007)

Colloids have increasingly been used to characterize or mimic many aspects of atomic and molecular systems. With confocal microscopy these colloidal particles can be tracked spatially in three dimensions with great precision over large time scales. This review discusses equilibrium phases such as crystals and liquids, and non-equilibrium phases such as glasses and gels. The phases that form depend strongly on the type of particle interaction that dominates. Hard-sphere-like colloids are the simplest, and interactions such as the attractive depletion force and electrostatic repulsion result in more non-trivial phases which can better model molecular materials. Furthermore, shearing or otherwise externally forcing these colloids while under microscopic observation helps connect the microscopic particle dynamics to the macroscopic flow behaviour. Finally, directions of future research in this field are discussed.
Modern Communication Circuits (1997)

From the Publisher:
This text introduces many of the fundamental circuit concepts used in modern receivers and transmitters. By foregoing detailed mathematical treatment, it emphasizes convenient and effective approximations for the analysis and design of communication circuits. Computerized circuit simulation methods are used throughout to facilitate detailed circuit analysis.
Monoclonal antibodies to mitotic cells. (1983)

Certain proteins or activities are present in mitotic cells but not in interphase cells. These proteins may be synthesized or activated, or both, just prior to mitosis and are responsible for the breakdown of the nuclear envelope and the condensation of chromosomes. To learn more about the nature of these proteins, we raised monoclonal antibodies to mitotic cells. Spleen cells from mice immunized with a 0.15 M NaCl extract of synchronized mitotic HeLa cells were fused with SP2/0-Ag14 mouse myeloma cells, and hybrids were selected in medium containing hypoxanthine, methotrexate, thymidine, and glycine. Two different hybridoma clones secreting antibodies reactive with mitotic and meiotic cells from every species tested were isolated. Chromosomes as well as cytoplasm in mitotic cells reacted with the antibodies, as detected by indirect immunofluorescence. The proteins from mitotic cells were separated by electrophoresis in NaDodSO4/polyacrylamide slab gels, transferred to nitrocellulose sheets, and stained immunochemically. The two antibodies, designated MPM-1 and MPM-2, recognize a family of polypeptides with apparent molecular masses of 0.40 to greater than 200 kilodaltons (kDa). Both antibodies reacted strongly with three polypeptide bands of 182 kDa, 118 kDa, and 70 kDa. Only mitotic cells exhibited the protein bands that were recognized by the antibodies. All these bands were found to be phosphoproteins as shown by 32P labeling and autoradiography and their removal by alkaline phosphatase treatment.
A Resource-Allocating Network for Function Interpolation (1991)

We have created a network that allocates a new computational unit whenever an unusual pattern is presented to the network. This network forms compact representations, yet learns easily and rapidly. The network can be used at any time in the learning process and the learning patterns do not have to be repeated. The units in this network respond to only a local region of the space of input values. The network learns by allocating new units and adjusting the parameters of existing units. If the network performs poorly on a presented pattern, then a new unit is allocated that corrects the response to the presented pattern. If the network performs well on a presented pattern, then the network parameters are updated using standard LMS gradient descent. We have obtained good results with our resource-allocating network (RAN). For predicting the Mackey-Glass chaotic time series, RAN learns much faster than do those using backpropagation networks and uses a comparable number of synapses.
4-Amino-1,8-naphthalimide: a novel inhibitor of poly(ADP-ribose) polymerase and radiation sensitizer (1999)

In living cells, ANI is about 1000-fold more potent at inhibiting PARP activity compared with 3-aminobenzamide (3-ABA). CFA studies demonstrated that ANI is a radiation sensitizer at non-toxic and lower concentrations (20 micromol x dm(-3)) than 3-ABA (10 mmol x dm(-3)).
Comparison of the EF-1 alpha and the CMV promoter for engineering stable tumor cell lines using recombinant adeno-associated virus. (2003)

This study underlines the importance of the promoter for the generation of stable cell lines. In addition it demonstrates that recombinant AAV can effectively be used as a gene delivery system for this purpose.
Detection of Circulating Tumor Cells in Prostate Cancer Patients: Methodological Pitfalls and Clinical Relevance (2009)

Disseminated malignancy is the major cause of prostate cancer-related mortality. Circulating tumor cells (CTCs) are essential for the establishment of metastasis. Various contemporary and molecular methods using prostate-specific biomarkers have been applied to detect extraprostatic disease that is undetectable by conventional imaging techniques, assessing the risk for disease recurrence after therapy of curative intent. However, the clinical relevance of CTC detection is still controversial. We review current literature regarding molecular methods used for the detection of CTCs in the peripheral blood and bone marrow biopsies of patients with prostate cancer, and we discuss the methodological pitfalls that influence the clinical significance of molecular staging.
The MALDI-TOF Mass Spectrometric View of the Plasma Proteome and Peptidome (2006)

Analyses of serum or plasma by MALDI-TOF MS provide new information mainly about small proteins and peptides with high molar abundance. The spectrum of observed proteins and peptides suggests value for applications such as assessment of cardiovascular risk, nutritional status, liver injury, kidney failure, and systemic immune responses rather than early detection of cancer. Extending analysis by MALDI-TOF MS to lower abundance components, such as markers for early-stage cancers, probably will require more extensive specimen fractionation before analysis.
Elevated catalase expression in a fungal pathogen is a double-edged sword of iron (2017)

Most fungal pathogens of humans display robust protective oxidative stress responses that contribute to their pathogenicity. The induction of enzymes that detoxify reactive oxygen species (ROS) is an essential component of these responses. We showed previously that ectopic expression of the heme-containing catalase enzyme in Candida albicans enhances resistance to oxidative stress, combinatorial oxidative plus cationic stress, and phagocytic killing. Clearly ectopic catalase expression confers fitness advantages in the presence of stress, and therefore in this study we tested whether it enhances fitness in the absence of stress. We addressed this using a set of congenic barcoded C. albicans strains that include doxycycline-conditional tetON-CAT1 expressors. We show that high basal catalase levels, rather than CAT1 induction following stress imposition, reduce ROS accumulation and cell death, thereby promoting resistance to acute peroxide or combinatorial stress. This conclusion is reinforced by our analyses of phenotypically diverse clinical isolates and the impact of stochastic variation in catalase expression upon stress resistance in genetically homogeneous C. albicans populations. Accordingly, cat1Δ cells are more sensitive to neutrophil killing. However, we find that catalase inactivation does not attenuate C. albicans virulence in mouse or invertebrate models of systemic candidiasis. Furthermore, our direct comparisons of fitness in vitro using isogenic barcoded CAT1, cat1Δ and tetON-CAT1 strains show that, while ectopic catalase expression confers a fitness advantage during peroxide stress, it confers a fitness defect in the absence of stress. This fitness defect is suppressed by iron supplementation. Also high basal catalase levels induce key iron assimilatory functions (CFL5, FET3, FRP1, FTR1). We conclude that while high basal catalase levels enhance peroxide stress resistance, they place pressure on iron homeostasis through an elevated cellular demand for iron, thereby reducing the fitness of C. albicans in iron-limiting tissues within the host.
Green Fluorescent Protein Variants as Ratiometric Dual Emission pH Sensors. 1. Structural Characterization and Preliminary Application (2002)

Novel dual emission, pH-sensitive variants of the green fluorescent protein (GFP) have been constructed and are suitable for ratiometric emission measurements in vivo. This new class of GFPs, termed deGPFs, results from substitution of wild-type residue 65 with threonine and residues 148 and/or 203 with cysteine. deGFPs display pK(a) values ranging from 6.8 to 8.0 and emission that switches from a green form (lambda(max) approximately 515 nm) to a blue form (lambda(max) approximately 460 nm) with acidifying pH. In this report we analyze in most detail the deGFP1 variant (S65T/H148G/T203C, pK(a) approximately 8.0) and the deGFP4 variant (S65T/C48S/H148C/T203C, pK(a) approximately 7.3). In the following paper [McAnaney, T. B., Park, E. S., Hanson, G. T., Remington, S. J., and Boxer, S. G. (2002) Biochemistry 41, 15489-15494], data obtained by ultrafast fluorescence upconversion spectroscopy can be described by a kinetic model that includes an excited-state proton-transfer pathway at high pH but not at low pH. Crystal structure analyses of deGFP1 at high-pH and low-pH conformations were performed to elucidate the basis for the dual emission characteristics. At low pH the structure does not contain a hydrogen bond network that would support rapid transfer of a proton from the excited state of the neutral chromophore to a suitable acceptor; hence blue emission is observed. At high pH, backbone rearrangements induced by changes in the associated hydrogen bond network permit excited-state proton transfer from the excited state of the neutral chromophore to the bulk solvent via Ser147 and bound water molecules, resulting in green emission from the anionic chromophore. Comparative analysis suggests that the basis for dual emission is elimination of the wild-type proton-transfer network by the S65T substitution, a general reduction in hydrogen-bonding opportunities, and a concomitant increase in the hydrophobic nature of the chromophore environment resulting from the cysteine substitutions. We evaluated the suitability of the deGFP4 variant for intracellular pH measurements in mammalian cells by transient expression in PS120 fibroblasts. The responses of deGFP4 and a commercially available pH-sensitive dye, SNARF-1, to changes in pH were compared in the same cells. Results show that the dynamic range of the emission ratio change is comparable between the two pH sensors over the range examined. Two-photon excitation was found to elicit a better deGFP4 fluorescent signal above cellular autofluorescence when compared to conventional confocal microscopy. Given their favorable optical characteristics, suitable pK(a)'s for the physiological pH range, and suitability for ratiometric measurements, dual emission GFPs should make excellent probes for studying pH in vivo.