gebhart/patrepeval huggingface dataset:
Dendritic cells stimulate primary human cytolytic lymphocyte responses in the absence of CD4+ helper T cells. (1990)

Cytotoxic lymphocytes are typically generated from unfractionated suspensions of human lymphocytes by stimulating with heterogeneous APCs and exogeneous growth factors. We have found that human blood dendritic cells can directly stimulate allogeneic human CD8+ T cells to proliferate and express antigen-specific cytotoxic activity. These primary responses, which are accompanied by the release of T cell growth factor(s), are induced in the absence of CD4+ helper T cells and are not inhibited by anti-CD4 mAb. Both antigen-specific CTL as well as nonspecific NK cells can be elicited by dendritic cells. The NK cell response can be depleted at the precursor level by panning with an anti-CD11b mAb, which removes a CD11b+/CD28-, CD16+ subset from the starting CD4- responders. Allogeneic blood monocytes are neither stimulatory nor inhibitory of these primary CD4- MLRs, even though monocytes present alloantigen in such a way as to be recognized as specific targets for CTL that have been sensitized by dendritic cells. The number of CD8+ cells that are blast transformed and express an activated phenotype (i.e., HLA DR/DQ+, CD25/IL-2R+, CD45R-) reaches 30-40% of the culture at day 4-5, the peak of the helper-independent response. We conclude that antigen-presentation by dendritic cells is sufficient in itself to prime cytolytic precursors. We speculate that using dendritic cell stimulators and CD4- responders in MLRs may be more efficient than standard tissue typing approaches for the detection of subtle, but important class I MHC-restricted histoincompatibilities in human transplantation.
“Where, O Death, Is Thy Sting?” A Brief Review of Apoptosis Biology (2010)

Apoptosis was a term introduced in 1972 to distinguish a mode of cell death with characteristic morphology and apparently regulated, endogenously driven mechanisms. The effector processes responsible for apoptosis are now mostly well known, involving activation of caspases and Bcl2 family members in response to a wide variety of physiological and injury-induced signals. The factors that lead of the decision to activate apoptosis as opposed to adaptive responses to such signals (e.g. autophagy, cycle arrest, protein synthesis shutoff) are less well understood, but the intranuclear Promyelocytic Leukaemia Body (PML body) may create a local microenvironment in which the audit of DNA damage may occur, informed by the extent of the damage, the adequacy of its repair and other aspects of cell status.
Responsive Photonic Crystals (2011)

This Review summarizes recent developments in the field of responsive photonic crystal structures, including principles for design and fabrication and many strategies for applications, for example as optical switches or chemical and biological sensors. A number of fabrication methods are now available to realize responsive photonic structures, the majority of which rely on self-assembly processes to achieve ordering. Compared with microfabrication techniques, self-assembly approaches have lower processing costs and higher production efficiency, however, major efforts are still needed to further develop such approaches. In fact, some emerging techniques such as spin coating, magnetic assembly, and flow-induced self-assembly have already shown great promise in overcoming current challenges. When designing new systems with improved performance, it is always helpful to bear in mind the lessons learnt from natural photonic structures.
Effects of acute volume loading and hemorrhage on intestinal vascular capacitance: a mechanism whereby capacitance modulates cardiac output. (2002)

A sigmoid function curve defined the relationship between cardiac output and IBV. Cardiac output remained constant over a wide range (between approximately 95% and 135% of control IBV). Outside this range, insufficient dilation or constriction resulted in a marked increase or decrease in venous pressures and cardiac output. These data indicate that vasculature capacitance modulates cardiac output during acute volume loading and hemorrhage, thereby maintaining cardiac output relatively constant over a wide range of total vascular blood volume.
An open study of B lymphocyte depletion in systemic lupus erythematosus (2002)

This study provides sufficient evidence for the safety and possible efficacy of B lymphocyte depletion therapy in SLE to justify a formal controlled trial.
Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As ofPorphyromonas gingivalis (2007)

Porphyromonas gingivalis is a Gram-negative anaerobic oral black-pigmented bacterium closely associated with chronic periodontitis. Lipopolysaccharide (LPS) derived from P. gingivalis is shown to be unusual because the LPS contains a greater number of lipid A species, such as tri-, tetra-, and/or penta-acylated lipid As. In this study, a lipid A possessing penta-fatty acyl chains derived from P. gingivalis strain 381 (compound PG-381-5FA) was synthesized, and examined for its immunobiological activities, compared with a tri-acylated lipid A (compound PG-381-3FA) synthesized previously. Compound PG-381-5FA, similar to compound PG-381-3FA, demonstrated weaker activity in a Limulus test as compared with Escherichia coli-type synthetic lipid A (compound 506). Compound PG-381-5FA, followed by compound PG-381-3FA, induced KC, interleukin-6, and tumour necrosis factor-alpha production in peritoneal macrophages from LPS-responsive C3H/HeN mice, but not in those from LPS-hyporesponsive C3H/HeJ mice. Furthermore, compound PG-381-5FA, as well as compound PG-381-3FA, activated nuclear factor-kappaB via Toll-like receptor (TLR)4/mD-2, but not TLR2, in a manner similar to compound 506, and worked as an antagonist for compound 506-induced cell activation. In the case of human peripheral blood mononuclear cells, compound PG-381-5FA showed much stronger IL-6-inducing activity than compound PG-381-3FA. The present results demonstrate that the chemical synthesis of a penta-acylated lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, is attributable to immune cell activation through TLR4, similar to that of compound 506.
Solar thermophotovoltaic using Al/sub 2/O/sub 3//Er/sub 3/Al/sub 5/O/sub 12/ eutectic composite selective emitter (2002)

Thermal emission properties of Al/sub 2/O/sub 3//Er/sub 3/Al/sub 5/O/sub 12/ eutectic composite are studied for the application of selective emitter of thermophotovoltaic (TPV) power generator. Since this material has a unique structure, high mechanical performance would be expected. Selective emission bands at wavelength 1.5 /spl mu/m due to Er/sup 3+/ ions are observed. Since these emission bands match up the sensitive region of GaSb PV cell, Al/sub 2/O/sub 3//Er/sub 3/Al/sub 5/O/sub 12/ eutectic composite is a suitable emitter material for TPV systems. Solar TPV system with a dish-type solar concentrator (diameter=1.56 m) has been made and tested using the selective emitter material. The performance and component temperature are studied for the system equipped with broad band SiC and Al/sub 2/O/sub 3//Er/sub 3/Al/sub 5/O/sub 12/ eutectic composite selective emitters. Low thermal load for TPV optical components is confirmed for the selective emitter system. The improvement of fill factor of GaSb PV cells is also observed for selective emitter system.
Formation of 3D micro- and nanostructures using liquid crystals as a template (2008)

There are two main approaches to form structures in the nanotechnology field of research, top-down and bottom-up. The top down approach uses machines to create nanostructures without control at the atomic level. Examples of top down mechanisms are photolithography, two-photon lithography, holography, electron beam lithography photoembossing and techniques originally developed for imaging purposes such as scanning tunneling microscopy and atomic force microscopy. The bottom-up approach uses the self-assembling properties of some materials, starting with atoms and molecules as building blocks to build up nanostructures. Common materials used in bottom-up approaches are block-copolymers, colloids, amphiphiles and liquid crystals. The top-down approaches have the disadvantage of not achieving control at the molecular level while the bottom-up approaches fail when trying to assemble them in bigger and more complex structures because of the randomness of the self assembly. This research focused on combining both types of approaches to overcome their limitations. We use liquid crystals (LCs) as self assembling materials and holography and lithography for the top-down techniques. The LC materials used contain reactive moieties which make them susceptible for polymerization. Usually the method of choice to polymerize LC is photopolymerization, because the temperature within certain limits can be freely chosen establishing that the molecular order associated to a particular LC phase is maintained during the process. A photoinitiator, a molecule that dissociates when exposed to light with the proper wavelength, is used to initiate the polymerization reaction. In common lithography a mask determines which areas will be exposed and thus polymerized. Our new technique, however, makes use of a new kind of material, a dichroic photoinitiator. The dissociation of this material is dependent of the polarization light that is used for excitation which must be parallel to the transition moment of the initiator molecule, i.e. for our rod-like shaped photoinitiator molecules parallel to their longitudinal axis. As the rod-like initiator molecules also align with their host LC molecules, polymerization can be controlled locally by LC orientation without the use of a mask or interference. Among other types of LC order the periodic orientation of cholesteric LC materials makes them perfect as a template for nanostructuring and microstructuring with a dichroic photoinitiator. The size of the created structures is determined by the cholesteric pitch and the cholesteric pitch can be easily modified by changing the concentration of its chiral dopant. This thesis presents an in depth characterization of the dichroic photoinitiators, as well as the creation of two and three dimensional microstructures by means of using the techniques previously mentioned.
GRAFT REJECTION IN RECIPIENTS OF T-CELL-DEPLETED HLA-NONIDENTICAL MARROW TRANSPLANTS FOR LEUKEMIA (1987)

Clinical trials with bone marrow depleted of donor T lymphocytes indicate that both the incidence and severity of graft-versus-host disease (GVHD) in patients undergoing bone marrow transplantation (BMT) for treatment of leukemia are greatly reduced. However, there has been a concurrent increase in the incidence of graft rejection, particularly among recipients of HLA-nonidentical marrow grafts. In order to investigate the nature of graft failure, peripheral blood mononuclear cells (PBMC) present at the time of graft failure have been characterized by phenotypic and functional analyses in 5 recipients of HLA-nonidentical marrow grafts. Rejection of HLA-nonidentical marrow grafts was associated with the emergence of host-derived T lymphocytes in all 5 patients. In 3 of these patients, the cells could be tested directly for cell-mediated cytotoxicity. Antidonor cytotoxicity was detected in each of these 3 patients. In one patient the target specificity of the cytotoxic lymphocytes was identified as the donor class I HLA antigen, HLA-B7. None of the patient PBMC mediated cytotoxicity against the natural killer cell target K562.
CMS subtypes characterized by high TMB shows immunosuppressive microenvironment that implies resistance to immunotherapy. (2019)

610 Background: Tumor mutational burden (TMB) is emerging as an important biomarker for immune checkpoint therapy (ICT) response. Yet even in the context of high TMB, ICT are likely ineffective in an immuno-suppressed microenvironment. Here we demonstrate that a well-characterized subtype of CRC, CMS2, associated with Wnt pathway activation, is immunosuppressive despite high TMB. Methods: Tumor/normal-paired DNAseq (WGS or WES) and deep RNAseq (∼200x10 6 reads per tumor) was performed on 464 GI tumors from a commercial database. Samples were classified as high TMB if they had &gt; 200 non-synonymous exonic mutations as previously established (Rizvi et al, 2015). Each sample was assigned to one of the colorectal Consensus Molecular subtypes (CMS) based on RNA classification. A curated panel of 109 genes that discriminate between 22 immune subsets was identified. For each of these immune signatures, a database containing 1880 unselected tumors was used to define a distribution of expression. The study samples were then scored for their deviances within such distributions. Significant enrichment was analyzed between immune subsets, CMS types, TMB status, and somatic mutational status. Results: Compared to other subtypes, CMS1 &amp; CMS2 were significantly high-TMB (adj. p &lt; 3.8E-4 &amp; p &lt; 4.7E-3 respectively). Perplexingly, CMS2 had significantly lower expression of 11 well-established checkpoint and TME markers including LAG3 and PDL1 (adj. p 1.5E-2 &amp; 2.9E-9 respectively), while CMS1 (MSI-enriched) expresses selected TME markers more than other subtypes (PDL1 adj. p &lt; 4.0E-6 &amp; LAG3 adj. p &lt; 1.0E-6). As expected, CMS2 tumors were significantly enriched for likely pathogenic variants in the Wnt-associated gene APC (adj. p &lt; 1.3E-8). Immune-deconvolution indicated substantial exclusion of Tem cells from CMS2 tumors, in line with Wnt/b-catenin blockade of TcmàTem maturation for immunoreactivity. Conclusions: The most common subtype of CRC, CMS2 (~37%), is highly immunosuppressive despite high TMB. ICT is only effective in an immunologically active microenvironment. TMB alone as a biomarker likely is insufficient to indicate the effectiveness of immunotherapy.
The Relationship between Individual Histologic Features and Disease Progression in Idiopathic Pulmonary Fibrosis (2002)

We have retrospectively studied 53 patients with idiopathic pulmonary fibrosis and a histologic diagnosis of usual interstitial pneumonia and evaluated the prognostic significance of four individual histologic features (fibroblastic foci [FF], interstitial mononuclear cell infiltrate, established fibrosis, and intra-alveolar macrophages) using a semiquantitative scale of 0-6. An objective count of FF was also undertaken. Using weighted kappa coefficients, interobserver agreement between pathologists was moderate to good (0.56-0.76). Subjective and objective FF scores were strongly associated (R(S) = 0.88, < 0.00005). Mortality was independently linked to a high FF score, p = 0.006, and a low percent predicted carbon monoxide diffusing capacity (DL(CO)), p = 0.01. For pulmonary function, on univariate analysis, the strongest correlations were observed between increasing interstitial mononuclear cell infiltrate or FF scores and greater declines in forced vital capacity (FVC) or DL(CO) at 6 months. Multivariate models revealed that increasing FF scores were independently associated with greater declines in FVC and DL(CO) at both 6 and 12 months. Increasing interstitial mononuclear cell infiltrate scores were also independently linked to functional decline, but only at 6 months. These data suggest a reproducible method on biopsy for predicting rate of disease progression in patients with idiopathic pulmonary fibrosis.
Poly r(C) Binding Protein-1 is Central to Maintenance of Cancer Stem Cells in Prostate Cancer Cells (2015)

Our proteomic profiling and subsequent validation indicate that PCBP1 is central to CSCs enrichment and functionality in prostate cancer.
Assessing the Corrosion Resistance of Nonequilibrium Magnesium-Yttrium Alloys (1995)

Magnesium-yttrium (Mg-Y) alloys containing 7 at% to 26 at% solute were fabricated using magnetron cosputter deposition. X-ray diffraction (XRD) revealed that no second phases were present in any of the alloys and that all but two of the alloys (Mg-7% Y and Mg-14% Y) were nanocrystalline and/or amorphous. Anodic potentiodynamic polarization performed in 0.1 M sodium chloride (NaCl) at both near-neutral and high pH values showed improved anodic polarization behavior for most of the alloys when compared to either pure Mg or one of the most corrosion-resistant commercial Mg alloys (alloy WE43 [UNS M18430]). In the high-pH solution, it was not uncommon for breakdown potentials (Eb) of the Mg-Y alloys to be 2,000 mV higher than values for alloy WE43. Long-term galvanic and potentiostatic testing was performed on selected alloys to verify anodic polarization behavior. Potentiostatic testing also was performed in a pH 12 buffer solution. When defects did not affect corrosion behavior, low current density values were obtained, with one specimen exhibiting a current density of 0.9 μA/cm2 (5.8 μA/in.2) at a potential &amp;gt; 300 mVSCE. X-ray photoelectron spectroscopy (XPS) conducted on Mg-22% Y revealed Y was enriched significantly in the passive film once the alloy was immersed in solution. This presence of oxidized Y in the passive film was believed to be responsible for the exceptional corrosion resistance of these alloys.
Transgenic potato plants resistant to the phytopathogenic bacterium Erwinia carotovora (1993)

The phytopathogenic bacterium Erwina carotovora spp. which infects potato plants causes severe losses in agriculture. No protective means or resistance traits usable for plant breeding are known. Introduction of a new resistance gene into potato by gene technology leads to a reduced susceptibility of the transgenic plants towards Erwinia carotovora atroseptica infection. Bacteriophage T4 lysozyme is the most active member of a class of bacteriolytic enzymes also detected in several plant species. Secretion of the foreign T4 lysozyme into the intercellular spaces of transgenic potato plants effects a resistance against the phytopathogenic bacterium already at low expression levels.
Increased erythrocyte phosphatidylserine exposure in sickle cell disease: flow-cytometric measurement and clinical associations (1996)

Increased exposure of phosphatidylserine (PS) in erythrocytes has been postulated to contribute to the pathophysiology of sickle cell disease because of its possible effects on blood coagulation, cell adhesion, and cell clearance. We developed a flow-cytometric assay to measure exposure of PS on the outer face of the erythrocyte membrane based on addition of fluorescein-annexin V to whole-blood specimens. The assay correlated linearly with binding of 125I-annexin V (r2 = .95, n = 125 samples). Normal donors (n = 30) showed virtually no annexin-positive cells (0.34% +/- 0.18% for 24-hour old samples). In contrast, annexin V binding was above the upper limit of normal in 96% of 205 specimens from 17 adult sickle cell and 2 beta-thalassemia patients; the mean percentage of annexin-positive cells was 2.86% +/- 2.00% (range, 0.4% to 12.0%). Values varied substantially over time for some patients, and mean values varied between patients. The percentage of annexin-positive cells always decreased after transfusion (11 events in 6 patients), and out of proportion to the amount of blood transfused. In conclusion, increased exposure of PS on a subpopulation of erythrocytes in vivo is a virtually universal feature of sickle cell disease, and its measurement may be useful to evaluate clinical status and response to therapeutic measures such as blood transfusion.
The spliced leader-associated RNA is a trypanosome-specific sn(o) RNA that has the potential to guide pseudouridine formation on the SL RNA (2002)

The spliced leader-associated (SLA1) RNA is a trypanosome-specific small RNA with unknown function. SLA1 carries a Sm-like site, and is associated with core Sm proteins. Here we found that SLA1 belongs to a family of hairpin-containing RNAs that are implicated in directing pseudouridylation. A potential for base-pair interaction between SLA1 and spliced leader (SL) RNA agrees with the canonical rules for guiding pseudouridylation on SL RNA. Direct RNA analysis showed that this uridine is indeed pseudouridylated in the SL RNA of Leptomonas collosoma, Leishmania major, and Trypanosoma brucei. This position is conserved in all trypanosomatid SL RNAs. Mutations introduced in the SL RNA to disrupt the interaction domain of SLA1/SL RNA abolished the formation of the pseudouridine. SLA1 is localized both to the nucleolus and nucleoplasm. This study solves a long-standing question regarding the function of this novel RNA and describes the first H/ACA RNA, which, unlike all other pseudouridine guides, is also a bona fide snRNA.
Function of Oxidative Cross-Linking of Cell Wall Structural Proteins in Plant Disease Resistance (1994)

Louise F. Brisson, Raimund Tenhaken, Chris Lamb, Function of Oxidative Cross-Linking of Cell Wall Structural Proteins in Plant Disease Resistance, The Plant Cell, Vol. 6, No. 12 (Dec., 1994), pp. 1703-1712
Diagenetic pyrite as a source for metals in orogenic gold deposits, Otago Schist, New Zealand (2012)

Abstract Framboidal diagenetic pyrite occurs in low‐grade turbidites on the northeast margin of the Otago Schist. Laser ablation inductively coupled plasma mass spectrometry (ICP‐MS) analyses of these framboids show that the main metals present, in addition to Fe, are As, Pb, Zn, Te, Ag and Mo; Au is present at between 0.5 and 2 ppm. Minor Au and As anomalies also occur sporadically in the turbidite matrix. Porphyroblastic pyrite at the nearby Macraes mine contains micron‐scale native gold and solid solution gold up to 30 ppm. These pyrite porphyroblasts are also enriched in As, W, Ni, Co and Bi. Lead, Zn, Te and Mo contents are distinctly lower than in the low‐grade framboids. These results show that low‐grade turbidites were a fertile source for Au and As for orogenic gold deposits such as Macraes. The pyrite to pyrrhotite transition, which occurred mainly under greenschist facies conditions, was probably the most effective As and Au mobilisation reaction during Mesozoic metamorphism.
A murine model for induction of long-term immunologic tolerance to factor VIII does not require persistent detectable levels of plasma factor VIII and involves contributions from Foxp3+ T regulatory cells (2009)

Under certain instances, factor VIII (FVIII) stimulates an immune response, and the resulting neutralizing antibodies present a significant clinical challenge. Immunotherapies to re-establish or induce long-term tolerance would be beneficial, and an in-depth knowledge of mechanisms involved in tolerance induction is essential to develop immune-modulating strategies. We have developed a murine model system for studying mechanisms involved in induction of immunologic tolerance to FVIII in hemophilia A mice. We used lentiviral vectors to deliver the canine FVIII transgene to neonatal hemophilic mice and demonstrated that induction of long-term FVIII tolerance could be achieved. Hemophilia A mice are capable of mounting a robust immune response to FVIII after neonatal gene transfer, and tolerance induction is dependent on the route of delivery and type of promoter used. High-level expression of FVIII was not required for tolerance induction and, indeed, tolerance developed in some animals without evidence of detectable plasma FVIII. Tolerance to FVIII could be adoptively transferred to naive hemophilia recipient mice, and FVIII-stimulated splenocytes isolated from tolerized mice expressed increased levels of interleukin-10 and decreased levels of interleukin-6 and interferon-gamma. Finally, induction of FVIII tolerance mediated by this protocol is associated with a FVIII-expandable population of CD4(+)CD25(+)Foxp3(+) regulatory T cells.