gebhart/patrepeval huggingface dataset:
Memory of mice and men: CD8+ T‐cell cross‐reactivity and heterologous immunity (2006)

The main functions of memory T cells are to provide protection upon re-exposure to a pathogen and to prevent the re-emergence of low-grade persistent pathogens. Memory T cells achieve these functions through their high frequency and elevated activation state, which lead to rapid responses upon antigenic challenge. The significance and characteristics of memory CD8+ T cells in viral infections have been studied extensively. In many of these studies of T-cell memory, experimental viral immunologists go to great lengths to assure that their animal colonies are free of endogenous pathogens in order to design reproducible experiments. These experimental results are then thought to provide the basis for our understanding of human immune responses to viruses. Although these findings can be enlightening, humans are not immunologically naïve, and they often have memory T-cell populations that can cross-react with and respond to a new infectious agent or cross-react with allo-antigens and influence the success of tissue transplantation. These cross-reactive T cells can become activated and modulate the immune response and outcome of subsequent heterologous infections, a phenomenon we have termed heterologous immunity. These large memory populations are also accommodated into a finite immune system, requiring that the host makes room for each new population of memory cell. It appears that memory cells are part of a continually evolving interactive network, where with each new infection there is an alteration in the frequencies, distributions, and activities of memory cells generated in response to previous infections and allo-antigens.
Blood Lactate is an Important Energy Source for the Human Brain (2009)

Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion (36 mumol per kg bw per min), and during 30 mins of cycling exercise at 75% of maximal oxygen uptake while the lactate infusion continued to establish arterial lactate concentrations of 0.89+/-0.08, 3.9+/-0.3, and 6.9+/-1.3 mmol/L, respectively. At rest, cerebral lactate utilization changed from a net lactate release of 0.06+/-0.01 to an uptake of 0.16+/-0.07 mmol/min during lactate infusion, with a concomitant decrease in the net glucose uptake. During exercise, the net cerebral lactate uptake was further increased to 0.28+/-0.16 mmol/min. Most (13)C-label from cerebral [1-(13)C]lactate uptake was released as (13)CO(2) with 100%+/-24%, 86%+/-15%, and 87%+/-30% at rest with and without lactate infusion and during exercise, respectively. The contribution of systemic lactate to cerebral energy expenditure was 8%+/-2%, 19%+/-4%, and 27%+/-4% for the respective conditions. In conclusion, systemic lactate is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.
Cellular basis of wall remodeling in long-term pressure overload-induced right ventricular hypertrophy in rats. (1988)

To determine the effects of long-term pressure overload on the structural mechanisms implicated in wall remodeling of the right ventricle, a mild pulmonary artery banding was applied to rats approximately 2 months old, and the animals were killed 150 days later. The surgical procedure resulted in a 60% reduction in the cross-sectional area of the constricted vessel and a 52% increase in the weight of the right ventricle. The hypertrophic myocardial response was associated with an elevation in right ventricular systolic pressure (from 33 +/- 11 mm Hg to 71 +/- 12 mm Hg), right ventricular end-diastolic pressure (from 3 +/- 1 mm Hg to 10 +/- 3 mm Hg), and central venous pressure (from 2 +/- 0.2 mm Hg to 10 +/- 3 mm Hg). The 76% increase in wall thickness after pulmonary artery stenosis was the result of a 24% lateral expansion of cardiac muscle cells and a 44% increase in the number of myocytes across the ventricular wall. The intermyocyte distance was also increased by 22%. These cellular adaptations occurred with no alterations in total myocyte length, average sarcomere length, and volume composition of the myocardium. Ventricular wall area was decreased by 14%, which suggests a small reduction in chamber volume. Myocyte growth was accompanied by proportional expansions of mitochondrial and myofibrillar components, so that the ratio of mitochondria to myofibrils in the cytoplasm remained essentially constant. In conclusion, ventricular remodeling in this model of chronic pressure hypertrophy is characterized by increases in cellular diameter and number that would both tend to decrease the magnitude of systolic and diastolic stresses on a per cell basis and thus improve the myocardial response to a prolonged and sustained mechanical load.
Derivation of Functional Endothelial Progenitor Cells from Human Umbilical Cord Blood Mononuclear Cells Isolated by a Novel Cell Filtration Device (2004)

Endothelial progenitor cells (EPCs) can differentiate from mononuclear cells (MNCs) of adult human peripheral blood, bone marrow, and cord blood during culture. Although MNCs are usually isolated by a Ficoll gradient centrifuge method, this method is time-consuming, and blood is easily contaminated. We developed a novel cell filtration device (StemQuickE, Asahi Kasei Medical, Oita, Tokyo, Japan) to isolate MNCs from human cord blood and examined whether functional EPCs could differentiate from MNCs isolated by this device. Recovery rates of MNCs, CD34(+) and CD133(+) progenitor cells, were significantly greater in the StemQuickE method than in the Ficoll method. During MNC culture, spindle-shaped attaching cells developed, and most of these cells incorporated DiI-acetylated low-density lipoprotein and showed positive binding to fluorescein isothiocyanate-lectin. Reverse transcription-polymerase chain reaction analysis revealed that attaching cells expressed various progenitor and endothelial lineage markers such as KDR, CD31, endothelial cell nitric oxide synthase, CD133, and LOX-1. Culture-expanded EPCs were isolated and labeled with a green fluorescent dye, PKH2-GL, and cocultured with human umbilical vein endothelial cells (HUVECs). EPCs formed angiogenesis-like networks together with HUVECs in 3D matrix gel. Finally, EPCs (3 x 10(5)) were implanted into ischemic hindlimb of nude rats (n = 3), and laser Doppler blood flowmetry (LDBF) revealed that the ratio of ischemic to normal limb LDBF was significantly greater in EPC-transplanted animals compared with controls receiving saline. In conclusion, the novel cell filtration device, StemQuickE, is a useful tool to isolate MNCs from human cord blood. Moreover, MNCs obtained by this filter system can give rise to functional EPCs.
Microlaser made of disordered media (2000)

We have fabricated microlasers with disordered semiconductor nanoparticles. The physical mechanism of optical confinement is based on Anderson localization of light in micrometer-sized random media. Pulsed lasing occurs around 380 nm at room temperature under optical pumping.
Fluorine-18 labeling of proteins. (1987)

Two fluorine-18-labeled reagents, methyl 3-[18F]fluoro-5-nitrobenzimidate and 4-[18F]fluorophenacyl bromide, have been prepared for covalent attachment of fluorine-18 to proteins. Both reagents can be prepared in moderate yields (30-50%, EOB) in synthesis times of 50-70 min. Reaction of these reagents with proteins (human serum albumin, human fibrinogen, and human immunoglobulin A) is pH independent, protein concentration dependent, and takes 5-60 min at mild pH (8.0) and temperature (25-37 degrees C), in yields up to 95% (corrected). The 18F-labeled proteins are purified by size exclusion chromatography.
Electrical Circuit Theory and Technology (2003)

Electrical Circuit Theory and Technology is a fully comprehensive text for courses in electrical and electronic principles, circuit theory and electrical technology. The coverage takes students from the fundamentals of the subject, to the completion of a first year degree level course. Thus, this book is ideal for students studying engineering for the first time, and is also suitable for pre-degree vocational courses, especially where progression to higher levels of study is likely. John Bird's approach, based on 700 worked examples supported by over 1000 problems (including answers), is ideal for students of a wide range of abilities, and can be worked through at the student's own pace. Theory is kept to a minimum, placing a firm emphasis on problem-solving skills, and making this a thoroughly practical introduction to these core subjects in the electrical and electronic engineering curriculum.This revised edition includes new material on transients and laplace transforms, with the content carefully matched to typical undergraduate modules.Free Tutor Support Material including full worked solutions to the assessment papers featured in the book will be available at https://textbooks.elsevier.com/. Material is only available to lecturers who have adopted the text as an essential purchase. In order to obtain your password to access the material please follow the guidelines in the book.
A Study of the Physical and Mechanical Properties of Paper Made fromAgave americanaL. Fibers (2011)

This article studies the influence of the pulping conditions of Agave americana L. [temperature (100–120°C), pulping time (60–120 mn) and soda concentration (4–8%)] on the pulp yield, kappa index, brightness, viscosity, and the hand sheets breaking length, tear index, and burst index. Responses of pulp and hand sheets properties to the process variables were analyzed using statistical software (Minitab 14). Pulp has been studied using a factorial design to identify the optimum operating conditions, equations relating the dependant variables to the operational variables of the pulping process were established. Results showed that acceptable physical and mechanical properties of pulps and paper could be achieved at 107°C, for 60 mn, and 6% of soda concentration. These are the most suitable conditions for obtaining paper sheets with a high breaking length and tear and burst indexes. Test sheets made from pulped agave leaf fibers were compared to paper made from other vegetable fibers (pine, agave tequilana, and eucalyptus fibers).
DdlN from Vancomycin-Producing Amycolatopsis orientalis C329.2 Is a VanA Homologue with d -Alanyl- d -Lactate Ligase Activity (1998)

Vancomycin-resistant enterococci acquire high-level resistance to glycopeptide antibiotics through the synthesis of peptidoglycan terminating in D-alanyl-D-lactate. A key enzyme in this process is a D-alanyl-D-alanine ligase homologue, VanA or VanB, which preferentially catalyzes the synthesis of the depsipeptide D-alanyl-D-lactate. We report the overexpression, purification, and enzymatic characterization of DdlN, a VanA and VanB homologue encoded by a gene of the vancomycin-producing organism Amycolatopsis orientalis C329.2. Evaluation of kinetic parameters for the synthesis of peptides and depsipeptides revealed a close relationship between VanA and DdlN in that depsipeptide formation was kinetically preferred at physiologic pH; however, the DdlN enzyme demonstrated a narrower substrate specificity and commensurately increased affinity for D-lactate in the C-terminal position over VanA. The results of these functional experiments also reinforce the results of previous studies that demonstrated that glycopeptide resistance enzymes from glycopeptide-producing bacteria are potential sources of resistance enzymes in clinically relevant bacteria.
α-Tocopherol decreases CD36 expression in human monocyte-derived macrophages (2001)

Cholesterol-laden macrophages are the hallmark of atherogenesis. The class B scavenger receptor, CD36, binds oxidized low density lipoprotein (OxLDL), is found in atherosclerotic lesions, and is upregulated by OxLDL. We tested the effects of alpha-tocopherol (AT) enrichment of human monocyte-derived macrophages on CD36 expression and cholesteryl ester accumulation. Monocytes isolated from normal volunteers were cultured into macrophages. Macrophages were enriched overnight with various doses of AT (25, 50, and 100 microM). LDL from normal volunteers was oxidized or acetylated (AcLDL) and incubated with macrophages for 48 h at a concentration of 50 or 100 microg/ml. CD36 expression was assessed by flow cytometry. Quantitative analysis of scavenger receptor class A (SR-A) activity was performed with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanide perchlorate (DiI)-labeled LDL. CD36 expression was maximal after 8;-10 days of culture. AT (> or =50 microM) significantly decreased CD36 expression upregulated by OxLDL and AcLDL (P < 0.01). Other antioxidants (beta- or gamma-tocopherol) or protein kinase C inhibitors failed to decrease CD36 expression. Concomitantly, DiI-AcLDL and DiI-OxLDL uptake was significantly decreased after AT treatment (P < 0.001). Cholesteryl ester accumulation was significantly decreased after AT enrichment (AcLDL + AT, 77% inhibition; OxLDL + AT, 42% inhibition). In conclusion, AT decreases both CD36 and SR-A expression and cholesteryl ester accumulation in human macrophages. This provides additional scientific support for the antiatherogenic properties of AT.
Elevated serum levels of interleukin 21 are associated with disease severity in patients with psoriasis (2012)

Serum IL-21 levels in patients with psoriasis are elevated and positively correlate with PASI scores. These results indicate that IL-21 may play an important role in the pathogenesis of psoriasis.
Different Levels of Immunogenicity of Two Strains of Fowlpox Virus as Recombinant Vaccine Vectors Eliciting T-Cell Responses in Heterologous Prime-Boost Vaccination Strategies (2006)

The FP9 strain of F has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recombinant modified V Ankara expressing the same antigen were evaluated for their ability to elicit T-cell responses against recombinant antigens from Plasmodium berghei (circumsporozoite protein) or human immunodeficiency virus type 1 (a Gag-Pol-Nef fusion protein). Gamma interferon enzyme-linked immunospot assay and fluorescence-activated cell sorting assays of the responses to specific epitopes confirmed the approximately twofold-greater cellular immunogenicity of FP9 compared to FPW, when given as the priming or boosting immunization. Equality of transgene expression in mouse cells infected with the two strains in vitro was verified by Western blotting. Directed partial sequence analysis and PCR analysis of FPW and comparison to available whole-genome sequences revealed that many loci that are mutated in the highly attenuated and culture-adapted FP9 strain are wild type in FPW, including the seven multikilobase deletions. These "passage-specific" alterations are hypothesized to be involved in determining the immunogenicity of fowlpox virus as a recombinant vaccine vector.
Human Fetal Mesenchymal Stem Cells as Vehicles for Gene Delivery (2005)

First-trimester fetal blood contains a readily expandable population of stem cells, human fetal mesenchymal stem cells (hfMSCs), which might be exploited for autologous intrauterine gene therapy. We investigated the self-renewal and differentiation of hfMSCs after transduction with onco-retroviral and lentiviral vectors. After transduction with either a MoMuLV retrovirus or an HIV-1-based lentiviral vector carrying the ss-galactosidase and green fluorescent reporter gene, respectively, transgene expression, self-renewal, and differentiation capabilities were assessed 2 and 14 weeks later. Transduction with the lentiviral vector resulted in higher efficiencies than with the MoMuLV-based vector (mean, 97.7 +/- 1.4% versus 80.2 +/- 5.4%; p = .02). Transgene expression was maintained with lentiviral-transduced cells (94.6 +/- 2.6%) but decreased over 14 weeks in culture with onco-retroviral-transduced cells (48.3 +/- 3.9%). The self-renewal capability of these cells and their ability to undergo osteogenic, adipogenic, and myogenic differentiation was unimpaired after transduction with either vector. Finally, clonal expansion of lentivirally modified cells was expanded over 20 population doublings with maintenance of multiline age differentiation capacity. These results suggest that hfMSCs may be suitable targets for ex vivo genetic manipulation with onco-retroviral or lentiviral vectors without affecting their stem cell properties.
Premature ovarian failure (2005)

Premature ovarian failure (POF) causing hypergonadotrophic hypogonadism occurs in 1% of women. In majority of cases the underlying cause is not identified. The known causes include: (a) Genetic aberrations, which could involve the X chromosome or autosomes. A large number of genes have been screened as candidates for causing POF; however, few clear causal mutations have been identified. (b) Autoimmune ovarian damage, as suggested by the observed association of POF with other autoimmune disorders. Anti-ovarian antibodies are reported in POF by several studies, but their specificity and pathogenic role are questionable. (c) Iatrogenic following surgical, radiotherapeutic or chemotherapeutic interventions as in malignancies. (d) Environmental factors like viral infections and toxins for whom no clear mechanism is known. The diagnosis is based on finding of amenorrhoea before age 40 associated with FSH levels in the menopausal range. Screening for associated autoimmune disorders and karyotyping, particularly in early onset disease, constitute part of the diagnostic work-up. There is no role of ovarian biopsy or ultrasound in making the diagnosis. Management essentially involves hormone replacement and infertility treatment, the only proven means for the latter being assisted conception with donated oocytes. Embryo cryopreservation, ovarian tissue cryopreservation and oocyte cryopreservation hold promise in cases where ovarian failure is foreseeable as in women undergoing cancer treatments.
Myeloid and Plasmacytoid Dendritic Cells Are Susceptible to Recombinant Adenovirus Vectors and Stimulate Polyfunctional Memory T Cell Responses (2007)

Although replication-incompetent recombinant adenovirus (rAd) type 5 is a potent vaccine vector for stimulating T and B cell responses, high seroprevalence of adenovirus type 5 (Ad5) within human populations may limit its clinical utility. Therefore, alternative adenovirus serotypes have been studied as vaccine vectors. In this study, we characterized the ability of rAd5 and rAd35 to infect and induce maturation of human CD11c(+) myeloid dendritic cells (MDCs) and CD123(+) plasmacytoid dendritic cells (PDCs), and their ability to stimulate Ag-specific T cells. Both MDCs and PDCs were found to express the primary receptor for Ad35 (CD46) but not Ad5 (coxsackie-adenovirus receptor; CAR). Both dendritic cell (DC) subsets were also more susceptible to rAd35 than to rAd5. MDCs were more susceptible to both rAd35 and rAd5 than were PDCs. Whereas rAd35 used CD46 for entry into DCs, entry of rAd5 may be through a CAR-independent pathway. Exposure to rAd35 but not rAd5 induced high levels of IFN-alpha in PDCs and phenotypic differentiation in both DC subsets. MDCs and PDCs exposed to either rAd5 or rAd35 encoding for CMV pp65 were able to present pp65 and activate CMV-specific memory CD8(+) and CD4(+) T cells in a dose-dependent manner, but MDCs stimulated the highest frequencies of pp65-specific T cells. Responding T cells expressed multiple functions including degranulation (CD107a surface mobilization) and production of IFN-gamma, IL-2, TNF-alpha, and MIP-1beta. Thus, the ability of rAd35 to naturally target important DC subsets, induce their maturation, and appropriately present Ag to T cells may herald greater in vivo immunogenicity than has been observed with rAd5.
Nuclear translocation of mitogen-activated protein kinase kinase (MEK1) in response to mitogenic stimulation (1997)

Mitogen-activated protein kinase kinase (MEK) is a dual-specificity protein kinase that is located primarily in the cellular cytosol, both prior to and upon mitogenic stimulation. The existence of a nuclear export signal in the N-terminal domain of MEK [Fukuda, M., Gotoh, I., Gotoh, Y. & Nishida, E. (1996) J. Biol. Chem. 271, 20024-20028] suggests that there are circumstances under which MEK enters the nucleus and must be exported. Using mutants of MEK, we show that the deletion of the nuclear export signal sequence from constitutively active MEK caused constitutive localization of MEK in the nucleus of COS7 and HEK-293T cells. However, when the same region was deleted from a catalytically inactive MEK, cytoplasmic localization was observed in resting cells, which turned nuclear upon stimulation. Confocal microscopy of COS7 cells expressing the above mutants showed localization of the active MEK in the nuclear envelope and also in the cell periphery. The differences in cellular localization between the wild-type and mutant MEKs are not due to severe changes in specificity because the recombinant, constitutively active MEK that lacked its N-terminal region exhibited the same substrate specificity as the wild-type MEK, both in vitro and in intact cells. Taken together, our results indicate that upon mitogenic stimulation, MEK, like extracellular signal responsive kinase and p90(RSK), is massively translocated to the nucleus. Rapid export from the nucleus, which is mediated by the nuclear export signal, is probably the cause for the cytoplasmic distribution observed with wild-type MEK.
Salvation in a Snippet of DNA? (1997)

Hopes are running high for vaccines made from nothing more than a bit of pathogen DNA. Often known as gene vaccines or naked DNA, DNA vaccines turned many heads in 1993, when researchers published the first reports about their ability to stimulate an immune response in mice. Instead of peptides, proteins, or viral vectors, DNA vaccines consist of nothing more than a gene from the pathogen, stitched into a circular stretch of bacterial DNA called a plasmid. In theory, these vaccines are simpler to make and can stimulate a broader immune response because they closely follow the cellular pathway traveled by the real pathogen. But how they work is still mysterious, and none has yet succeeded in a clinical trial.