gebhart/patrepeval huggingface dataset:
Pre-exposure of human B cells to recombinant IL-1 enhances subsequent proliferation. (1988)

The reported effects of the monocyte-derived cytokine IL-1 on human B lymphocytes are both varied and controversial. IL-1 has been reported to augment both proliferation and Ig secretion of previously activated human B cells. In the present study highly purified splenic B cells were cultured with rIL-1 before, simultaneously with, and after the addition of the polyclonal B cell mitogen, anti-Ig. rIL-1 had no significant effect on B cell proliferation when added simultaneously with or after B cell activation with anti-Ig. However, incubation of splenic B cells with rIL-1 for 24 h before stimulation with anti-Ig appeared to enhance mitogenesis. With the observation that rIL-1 exerted effects on resting B cells, the effect of rIL-1 on several events which accompany B cell activation was examined. rIL-1 failed to stimulate RNA synthesis, effect increases in cell size or intracellular Ca2+ levels, or lead to the hyperexpression of MHC class II or B cell activation Ag. These studies suggest that rIL-1 does not activate B cells but primes them to respond to subsequent activation.
Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization (2012)

Activated macrophages are described as classically activated or M1 type and alternatively activated or M2 type, depending on their response to proinflammatory stimuli and the expression of genetic markers including iNOS, arginase1, Ym1, and Fizz1. Here we report that Akt kinases differentially contribute to macrophage polarization, with Akt1 ablation giving rise to an M1 and Akt2 ablation resulting in an M2 phenotype. Accordingly, Akt2(-/-) mice were more resistant to LPS-induced endotoxin shock and to dextran sulfate sodium (DSS)-induced colitis than wild-type mice, whereas Akt1(-/-) mice were more sensitive. Cell depletion and reconstitution experiments in a DSS-induced colitis model confirmed that the effect was macrophage-dependent. Gene-silencing studies showed that the M2 phenotype of Akt2(-/-) macrophages was cell autonomous. The microRNA miR-155, whose expression was repressed in naive and in LPS-stimulated Akt2(-/-) macrophages, and its target C/EBPβ appear to play a key role in this process. C/EBPβ, a hallmark of M2 macrophages that regulates Arg1, was up-regulated upon Akt2 ablation or silencing. Overexpression or silencing of miR-155 confirmed its central role in Akt isoform-dependent M1/M2 polarization of macrophages.
A Therapeutic Antibody for Cancer, Derived from Single Human B Cells (2016)

Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery.
Atomic layer deposition of ultra-thin and smooth Al-doped ZnO for zero-index photonics (2018)

We report fabrication of smooth Al-doped ZnO (AZO) films <100 nm by atomic layer deposition (ALD) with epsilon-near-zero (ENZ) frequencies in the near-infrared region controlled by deposition parameters. Excitation of the ENZ plasmon-polariton mode in the AZO films is experimentally demonstrated. The ALD growth of smooth ultra-thin AZO nanolayers with tunable ENZ frequency enables the development of ultra-compact and tunable metamaterial devices and flat nonlinear/quantum zero-index optics.
The structure of human collagen type IX and its organization in fetal and infant cartilage fibrils. (1988)

Human collagen type IX was isolated from the media of organ cultures of fetal or infant hyaline cartilage. It consisted of three distinct, disulfide-bonded polypeptides of 115, 84, and 72 kDa, respectively. Digestion with chondroitinase ABC reduced the apparent molecular mass of the 115-kDa chain to about 65 kDa demonstrating that also human collagen type IX is a proteoglycan. In the electron microscope, the molecule had a rigid rod-like structure with characteristic kinks and with a globular domain at one end. Digestion of human collagen type IX with pepsin leads to somewhat heterogeneous fragments. Affinity-purified antibodies to the mixture of fragments specifically reacted with the fragment HMW without cross-reaction with chicken HMW. LMW of both species were recognized to the same low extent. Mechanically generated fibril fragments from human fetal cartilage were heterogeneous in diameter. Significantly, they could be immunostained for collagen type IX in a D-periodic pattern and regardless of the fibril diameter. Some fibrils were poorly labeled, again independently of the diameter. Therefore, the role of collagen type IX in cartilage probably is not to control directly the lateral growth during fibrillogenesis but rather to stabilize the fibril network.
Biologic treatment in Sjogren's syndrome (2014)

SS is a chronic systemic autoimmune disease characterized by decreased exocrine gland function. A variety of other disease manifestations may also be present, including general constitutional symptoms and extraglandular features. A multidisciplinary approach focused on both local and systemic medical therapies is needed as the disease has a wide clinical spectrum. The current treatment for SS is mainly symptomatic. However, there is evidence that systemic drugs are effective in controlling extraglandular manifestations of the disease. Overall evidence for the role of conventional immunosuppressive therapy is limited. A number of attempts to use biologic therapies have led to variable results. Biologic agents targeting B cells, such as rituximab, epratuzumab and belimumab, have shown promising results, but further studies are needed to validate the findings. Early-phase studies with abatacept and alefacept proved that T cell stimulation inhibition is another potentially effective target for SS treatment. Modulation or inhibition of other targets such as IFN, IL-6 and Toll-like receptor are also currently being investigated. We have summarized the available evidence regarding the efficacy of biologic treatments and discuss other potential therapies targeting pathways or molecules recognized as being involved in the pathogenesis of SS.
apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. (1993)

The major component of senile plaques found in the brains of Alzheimer disease patients is the beta-amyloid peptide, which is derived from a larger amyloid precursor protein (APP). Recently, a number of APP and APP-related proteins have been identified in different organisms and constitute the family of APP proteins. We have isolated several cDNAs encoding an APP-related protein in the nematode Caenorhabditis elegans and have designated the corresponding gene as apl-1. The apl-1 transcripts undergo two forms of posttranscriptional modification: trans-splicing and alternative polyadenylylation. In vitro translation of an apl-1 cDNA results in a protein of approximately the expected size. Similar to the Drosophila, human, and mouse APP-related proteins, APL-1 does not appear to contain the beta-amyloid peptide. Because APP-related proteins seem to be conserved through evolution, the apl-1 gene from C. elegans should be important for determining the normal function of human APP.
Dinámica del vacío en "La claridad desierta", de José Bergamín (1986)

Treatment-refractory fever during the first 10 days after subarachnoid hemorrhage (SAH) is predicted by poor clinical grade and intraventricular hemorrhage, and is associated with increased mortality and more functional disability and cognitive impairment among survivors. Clinical trials are needed to evaluate the impact of prophylactic fever control on outcome after SAH.
Nitric oxide release from normal and dysfunctional endothelium. (1999)

The endothelium plays a critical role in maintaining vascular tone by releasing vasoconstrictor and vasodilator substances. Endothelium - derived nitric oxide (NO) is a vasodilator rapidly inactivated by superoxide (O2-) found in significant quantities. The porphyrinic sensor (0.5-8 microm diameter) and chemiluminescence methods were used to measure NO and (O2-) respectively. Effects of hypertension, low density lipoprotein (LDL), and heart preservation on the release of NO and O2- were delineated. In the single endothelial cell (rat aorta) NO concentration was the highest in the cell membrane decreasing exponentially with distance from cell, and becoming undetectable beyond 50 microm and 25 microm for normotensive (WKY) and hypertensive (SHR) rats respectively. The endothelium of SHR released 40% less NO (300+/-25 nmol L(-1)) than that of normotensive rats (500+20 nmol L(-1)), due to the higher production of O2- in SHR rats. An exponentially decreasing NO production (from 1.20 +/- 0.15 to 0.16 +/- 0.05 micromol (L-1)) and concomitant increase of O2- generation (from 10 +/- 0.3 to 300 +/- 25 nmol L(-1) were observed in left ventricle of stored (eight hours) rabbit heart. Native and oxidized low density lipoproteins (nLDL and oxLDL) inhibited NO generation and increased O2- production. The local depletion of the L-arginine substrate may disarrange the nitric oxide synthase, leading to production of O2- from oxygen.
Diels–Alder Cycloadditions on Synthetic RNA in Mammalian Cells (2014)

Inverse electron demand Diels-Alder cycloadditions are extremely useful tools for orthogonal labeling of biomolecules such as proteins or small molecules in a cellular context. In-cell labeling of dienophile-modified RNA oligonucleotides using Diels-Alder cycloaddition reactions has not been demonstrated before. In this study we report site-specific labeling of RNA oligonucleotides modified with norbornene derivatives at a predefined sequence position within an RNA sequence in vitro and in mammalian cells using various tetrazine-fluorophore conjugates. The approach could in future be used as a chemical tool for the detection and investigation of RNA functions in cells minimizing the presumed distortion of RNA functions by a large chemical reporter group such as a fluorophore.
Pore formation and mitogenicity in blood cells by the class 2 protein of Neisseria meningitidis. (1992)

The class 2 outer membrane protein (MIEP) of Neisseria meningitidis has recently been shown to be mitogenic for lymphocytes (Liu, M.A., Friedman, A., Tai, J., Martinez, D., Deck, R. R., Hawe, L. A., Shieh, J. T.-C., Jenkins, T. D., Donnelly, J. J., and Oliff, A. I. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4633-4637. In this study, a possible connection between MIEP's mitogenicity and its possible action as a porin was investigated. MIEP, purified from the bacterial outer membrane protein complex under denaturing conditions, caused a modest but specific release of ions (86Rb) from both erythrocytes and lymphocytes, ultimately resulting in cell lysis. The dose-response of MIEP on erythrocyte lysis was qualitatively similar to a known porin (protein I from Neisseria gonorrhoeae) but was much less efficient. Induction or preservation of native structure in MIEP increased pore formation, resulting in levels comparable to that of the protein I porin. These observations suggest that native MIEP, free of the other outer membrane proteins of Neisseria meningitidis, can efficiently form pores in cells, but that denatured MIEP is variably and marginally effective. However, pore formation by MIEP was not related to its mitogenicity in lymphocytes, based on: (i) native MIEP was not mitogenic; (ii) denatured MIEP was highly mitogenic; and (iii) denatured MIEP was mitogenic at concentrations below the threshold level for pore formation. Therefore, mitogenicity is dependent upon MIEP being in a denatured, monomeric state and is masked by native conformation.
A 2.6 GB/s multi-purpose chip-to-chip interface (2002)

A high-speed interface cell delivers 800 Mb/s/pin data transfer rate on a 26b wide I/O interface consisting of a dual-byte data field and a byte-wide command field. For 2.6 GB/s data rate, a 400 MHz clock recovery circuit guarantees the timing margin for transferring 800 mV swing data at both clock edges over the I/O interface. Data from the high speed interface is internally deserialized to provide a 100 MHz (f/4) ASIC clock interface. A test chip contains three megacells and built-in clock synchronization circuits to ensure proper data transfer between the three megacells with minimal impact on latency. Controlled impedance buses, referred to as channels, with careful PCB layout ensure 800 Mb/s/pin data rate on-board for ASIC-to-ASIC or ASIC-to-DRAM system configuration.
El mito de la madre (1999)

Cuando hace casi cincuenta años Simone de Beauvoir (1981; II: 13) afirmó: “no se nace mujer: llega una a serlo”, aludió a los múltiples y Ccomplejos procesos socioculturales de meticulosa y disciplinada socialización de lo femenino, que como identidad social subalterna —construida a partir de un cuerpo sexuado— se relaciona, se contrasta y se define frente al sujeto genérico masculino. Simbolizada desde el imaginario androcéntrico como atada a las fuerzas naturales de lo precultural —como instinto en primera instancia— la mujer como producción histórica/cultural de los regímenes sexo/género patriarcales, oculta en los misterios aparentes de su ser reproductor la compleja red de influencias económicas, sociales y culturales que han accionado sobre su cuerpo y subjetividad, para traducir lo biológico de su naturaleza en una naturaleza eminentemente social.
CD40 ligand is a T cell growth factor (1993)

CD40 ligand (CD40L) is a 33-kDa type II membrane glycoprotein induced on T cells upon activation. CD40L has previously been shown to induce proliferation of resting B cells, immunoglobulin (Ig) secretion from B cells cultured with cytokines and cytokine secretion and tumoricidal activity from monocytes. In this report CD40L is shown to be stimulatory for human T cells, inducing CD25 (p55 IL-2R) and CD40L expression on resting peripheral blood T cells, enhanced expression of these molecules and CD69 on CD3-activated cells and secretion of interferon-gamma, tumor necrosis factor-alpha and interleukin (IL)-2 from T cells cultured in the presence of a sub-mitogenic concentration of phytohemagglutinin A (PHA). Furthermore, stimulation with CD40L induces proliferation of CD3- or PHA-activated T cells of blood, tonsillar or thymic origin. A similar proliferative response is observed with CD4+ and CD8+ T cells and this effect is largely IL-2 independent. A soluble construct of the extracellular domain of the CD40L has similar activity to that of membrane-expressed ligand in the induction of T cell surface antigens and proliferation. The results presented here taken together with the various activities ascribed for CD40L on B cells and monocytes demonstrate that CD40L has pleiotropic biological activity for cells of the hemopoietic lineage.
Effects of ultraviolet radiation on the type-I collagen protein triple helical structure: A method for measuring structural changes through optical activity (2002)

A detailed study of the effects of ultraviolet radiation on type-I collagen has been conducted. We have confirmed that exposure to ultraviolet radiation lowers the denaturation temperature of type-I collagen and that the triple helical state is destroyed provided that the radiation dose exceeds a threshold level, which is defined as the incident radiation dose that raises the sample temperature above the (lower) denaturation temperature. For incident radiation doses below threshold, the collagen molecule remains in a triple helical state. Denaturation is determined by changes in the optical activity of the collagen solution. Furthermore, a new instrument has been developed and tested to measure the optical rotatory dispersion properties of chiral molecules. The advantage of this instrument is that it enables a real-time measurement of the optical activity of chiral macromolecules while exposing samples to ultraviolet radiation and requiring no special sample preparation techniques. Using a differential measurement scheme, system errors have been minimized.
Identification of interleukin-13 receptor α2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma (2008)

Human malignant glioma cell lines and adult brain tumors overexpress high levels of interleukin-13 receptor alpha2 chain (IL-13Ralpha2). Because the IL-13Ralpha2 chain is an important target for cancer therapy and prognosis for patients with brainstem glioma (BSG) remains dismal, we investigated the expression of this receptor in specimens of diffusely infiltrative pediatric BSG relative to normal brain tissue. Twenty-eight BSG specimens and 15 normal brain specimens were investigated for IL-13Ralpha2 protein expression by immunohistochemical analysis (IHC) using two different antibodies in two different laboratories. Highly sensitive Q-dot-based IHC and in situ hybridization (ISH) assays were also developed to identify IL-13Ralpha2 protein and RNA in these specimens. The results were evaluated independently in two laboratories in a blinded fashion. By Q-dot IHC or a standard IHC assay, 17 of 28 (61%) tumor specimens showed modest to strong staining for IL-13Ralpha2, while 15 normal brain tissue samples showed weak expression for IL-13Ralpha2 protein. Significant interrater agreement between the two laboratories was seen in the assessment of IL-13Ralpha2 intensity. High-level IL-13Ralpha2 RNA expression was detected in tumor samples by Q-dot ISH, but only weak RNA expression was observed in normal brain. Significant agreement between ISH and IHC assays was observed (simple kappa [kappa] estimate=0.358, weighted kappa=0.89, p=0.001). IL-13Ralpha2 protein and mRNA are expressed to significantly higher levels in BSG than in normal brain tissue. Both IHC and ISH represent robust methods to detect expression of the IL-13Ralpha2 receptor in BSG that could represent an important new drug target for treatment of this disease.
Asymmetric catalytic reactions by NbO-type chiral metal–organic frameworks (2011)

Chiral metal–organic frameworks (MOFs) constitute a unique class of multifunctional hybrid materials and are envisioned as a versatile tool for various enantioselective applications, including the separation of optical isomers and the promotion of catalytic enantioselective reactions. Despite some pioneering works on catalytic enantioselective reactions promoted by chiral MOFs, there is still a need for practical catalysts and many fundamental issues must be answered; such as pin-pointing the site of the reaction and expedition of the reaction rate to the level of that in homogeneous media. We have designed and synthesized a chiral metal–organic framework, (S)-KUMOF-1 (Cu2(S)-1)2(H2O)2, 1 = 2,2′-dihydroxy-6,6′-dimethyl(1,1′-biphenyl)-4,4′-dicarboxylate) of which a non-interpenetrating NbO type framework provides a spacious pore (2 × 2 × 2 nm3) and is equipped with potential catalytic sites exposed into the pore. Since the functional group on the organic links, biphenols in this MOF, can be modified further on demand, this MOF can serve as a platform for new heterogeneous catalysis. Two reactions, the carbonyl-ene reaction with modified MOF after replacement of the protons on biphenol on the organic links with Zn(II) and the hetero-Diels–Alder reaction with Ti(IV), respectively, were studied. In this manoeuver, we observed that the reaction occurs entirely inside the pores and the reaction rate of the heterogeneous reaction by this specific MOF is comparable to that of its homogeneous counterpart. In addition, it is also observed that the enantioselectivities are significantly improved by extra steric bias provided from the frames of the MOF. These observations reinforce the legitimacy of the strategy of using a chiral MOF as a highly enantioselective heterogeneous catalyst.
An Immunoadhesin Incorporating the Molecule OX-2 Is a Potent Immunosuppressant That Prolongs Allo- and Xenograft Survival (1999)

We have established that, in mice receiving donor-specific immunization by the portal vein, the increased graft survival seen is associated with the increased expression of a molecule (OX-2) on a subpopulation of dendritic cells (DC), and polarization of cytokine production to type 2 cytokines on Ag-specific restimulation of cells from these mice. Furthermore, infusion of a mAb to OX-2 blocks both the increased graft survival and the altered cytokine production seen. We have constructed an immunoadhesin in which the extracellular domain of OX-2 is linked to the murine IgG2a Fc region, and we have expressed this molecule (OX-2:Fc) in a eukaryotic (baculovirus) expression system. Incubation of lymphocytes with 50 ng/ml OX-2:Fc inhibits a primary mixed lymphocyte reaction in vitro, as assayed by proliferation and induction of cytotoxic T cells, and also alters cytokine production with decreased IL-2 (IFN-gamma) production and increased IL-4 (IL-10) production. Similarly, in vivo infusion of OX-2:Fc promotes increased allo- and xenograft (both skin and renal grafts) survival and decreases the Ab response to sheep erythrocytes. Our data suggest this molecule might have clinical importance in allo- and xenotransplantation.
Differential regulation of the JE gene encoding the monocyte chemoattractant protein (MCP-1) in cervical carcinoma cells and derived hybrids (1994)

Malignant human papillomavirus type 18 (HPV18)-positive cervical carcinoma cells can be reverted to a nonmalignant phenotype by generation of somatic cell hybrids with normal human fibroblasts. Although nontumorigenic hybrids, their tumorigenic segregants, and the parental HeLa cells have similar in vitro properties, inoculation only of nontumorigenic cells into nude mice results in a selective suppression of HPV18 transcription which precedes cessation of cellular growth. Our present study, aimed at understanding the differential regulation in vitro and in vivo, shows that the JE gene, encoding the monocyte chemoattractant protein (MCP-1), is expressed only in nontumorigenic hybrids. Although the gene, including its regulatory region, is intact, no JE (MCP-1) mRNA is detected in the tumorigenic segregants and in other malignant HPV-positive cervical carcinoma cell lines. Tests of several monocyte-derived cytokines showed that only tumor necrosis factor alpha strongly induces the JE (MCP-1) gene in nontumorigenic cells and that this is accompanied by a dose-dependent reduction of HPV transcription. The JE (MCP-1) up-regulation occurs within 2 h and does not require de novo protein synthesis. The response to tumor necrosis factor alpha seems to be mediated by an NF-kappa B-related mechanism, since the induction can be completely abrogated by pretreating the cells with an antioxidant such as pyrrolidine dithiocarbamate. Interestingly, cocultivation of nonmalignant hybrids with monocyte-enriched fractions from human peripheral blood also results in an induction of the JE (MCP-1) gene and a concomitant suppression of HPV18 transcription. Neither effect is observed in malignant cells. These data suggest that JE (MCP-1) may play a pivotal role in the intercellular communication by triggering an intracellular pathway which negatively interferes with viral transcription in HPV-positive nontumorigenic cells.
Isolation ofHelicobacter mustelaeit from ferrets in New Zealand (2000)

Helicobacter mustelae is not exotic to New Zealand, but is present in two populations of ferrets tested in the North Island.