gebhart/patrepeval huggingface dataset:
Contribution of Regulatory T Cells and Effector T Cell Deletion in Tolerance Induction by Costimulation Blockade (2008)

Blocking of costimulatory signals for T cell activation leads to tolerance in several transplantation models, but the underlying mechanisms are incompletely understood. We analyzed the involvement of regulatory T cells (Treg) and deletion of alloreactive cells in the induction and maintenance of tolerance after costimulation blockade in a mouse model of graft-vs-host reaction. Injection of splenocytes from the C57BL/6 parent strain into a sublethally irradiated F(1) offspring (C57BL/6 x C3H) induced a GVHR characterized by severe pancytopenia. Treatment with anti-CD40L mAb and CTLA4-Ig every 3 days during 3 wk after splenocyte injection prevented disease development and induced a long-lasting state of stable mixed chimerism (>120 days). In parallel, host-specific tolerance was achieved as demonstrated by lack of host-directed alloreactivity of donor-type T cells in vitro and in vivo. Chimerism and tolerance were also obtained after CD25(+) cell-depleted splenocyte transfer, showing that CD25(+) natural Treg are not essential for tolerance induction. We further show that costimulation blockade results in enhanced Treg cell activity at early time points (days 6-30) after splenocyte transfer. This was demonstrated by the presence of a high percentage of Foxp3(+) cells among donor CD4(+) cells in the spleen of treated animals, and our finding that isolated donor-type T cells at an early time point (day 30) after splenocyte transfer displayed suppressive capacity in vitro. At later time points (>30 days after splenocyte transfer), clonal deletion of host-reactive T cells was found to be a major mechanism responsible for tolerance.
Coordinating cellular background transfers using loadsense (2013)

To minimize battery drain due to background communication in cellular-connected devices such as smartphones, the duration for which the cellular radio is kept active should be minimized. This, in turn, calls for scheduling the background communication so as to maximize the throughput. It has been recognized in prior work that a key determinant of throughput is the wireless link quality. However, as we show here, another key factor is the load in the cell, arising from the communication of other nodes. Unlike link quality, the only way, thus far, for a cellular client to obtain a measure of load has been to perform active probing, which defeats the goal of minimizing the active duration of the radio.
Electrospun poly(L-lactide-co-glycolide) biodegradable polymer nanofibre tubes for peripheral nerve regeneration (2004)

10.1088/0957-4484/15/11/014
Immune checkpoint proteins: exploring their therapeutic potential to regulate atherosclerosis (2017)

Abstract The immune system provides a large variety of immune checkpoint proteins, which involve both costimulatory and inhibitory proteins. Costimulatory proteins can promote cell survival, cell cycle progression and differentiation to effector and memory cells, whereas inhibitory proteins terminate these processes to halt ongoing inflammation. Immune checkpoint proteins play a pivotal role in atherosclerosis by regulating the activation and proliferation of various immune and non‐immune cells, such as T‐cells, macrophages and platelets. Upon activation within the atherosclerotic lesions or in secondary lymphoid organs, these cells produce large amounts of pro‐atherogenic cytokines that contribute to the growth and destabilization of lesions, which can result in rupture of the lesion causing acute coronary syndromes, such as a myocardial infarction. Given the presence and regulatory capacity of immune checkpoint proteins in the circulation and atherosclerotic lesions of cardiovascular patients, modulation of these proteins by, for example, the use of monoclonal antibodies, offers unique opportunities to regulate pro‐inflammatory immune responses in atherosclerosis. In this review, we highlight the latest advances on the role of immune checkpoint proteins, such as OX40–OX40L, CTLA‐4 and TIM proteins, in atherosclerosis and discuss their therapeutic potential as promising immunotherapies to treat or prevent cardiovascular disease. Linked Articles This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc
In vivobubble nucleation probability in sheep brain tissue (2011)

Gas nuclei exist naturally in living bodies. Their activation initiates cavitation activity, and is possible using short ultrasonic excitations of high amplitude. However, little is known about the nuclei population in vivo, and therefore about the rarefaction pressure required to form bubbles in tissue. A novel method dedicated to in vivo investigations was used here that combines passive and active cavitation detection with a multi-element linear ultrasound probe (4-7 MHz). Experiments were performed in vivo on the brain of trepanated sheep. Bubble nucleation was induced using a focused single-element transducer (central frequency 660 kHz, f-number = 1) driven by a high power (up to 5 kW) electric burst of two cycles. Successive passive recording and ultrafast active imaging were shown to allow detection of a single nucleation event in brain tissue in vivo. Experiments carried out on eight sheep allowed statistical studies of the bubble nucleation process. The nucleation probability was evaluated as a function of the peak negative pressure. No nucleation event could be detected with a peak negative pressure weaker than -12.7 MPa, i.e. one order of magnitude higher than the recommendations based on the mechanical index. Below this threshold, bubble nucleation in vivo in brain tissues is a random phenomenon.
Genome-wide Analysis of Simultaneous GATA1/2, RUNX1, FLI1, and SCL Binding in Megakaryocytes Identifies Hematopoietic Regulators (2011)

Hematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development of individual lineages. Here, we report the genome-wide binding sites for the five key hematopoietic transcription factors--GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL--in primary human megakaryocytes. Statistical analysis of the 17,263 regions bound by at least one factor demonstrated that simultaneous binding by all five factors was the most enriched pattern and often occurred near known hematopoietic regulators. Eight genes not previously appreciated to function in hematopoiesis that were bound by all five factors were shown to be essential for thrombocyte and/or erythroid development in zebrafish. Moreover, one of these genes encoding the PDZK1IP1 protein shared transcriptional enhancer elements with the blood stem cell regulator TAL1/SCL. Multifactor ChIP-Seq analysis in primary human cells coupled with a high-throughput in vivo perturbation screen therefore offers a powerful strategy to identify essential regulators of complex mammalian differentiation processes.
Calorimetric Measurement of Surface and Interface Enthalpies of Yttria-Stabilized Zirconia (YSZ) (2010)

The surface and interface enthalpies of cubic stabilized zirconia solid solutions containing 8, 10, and 12 mol % Y2O3 were determined by a combination of calorimetric, morphological, and structural analyses techniques. Nanocrystalline samples with several surface areas and degrees of agglomeration were synthesized by simultaneous precipitation and annealing at temperatures of 470−900 °C. Samples were characterized by X-ray diffraction and Raman spectroscopy. Surface areas were measured by N2 adsorption, and interface areas were estimated by comparing surface areas from N2 adsorption to those derived from an analysis of the crystallite sizes refined from X-ray diffraction data. Calorimetric measurements of heat of solution in a sodium molybdate melt, as a function of surface and interface areas, enabled us to experimentally derive trends in the surface and interface enthalpies of hydroxylated surfaces. Accounting for heats of water adsorption measured by microcalorimetry allowed us to obtain the surface enthalpies (energies) of the anhydrous surfaces at each composition. Average surface enthalpies were determined to increase with yttria content, from 0.85 ± 0.07 J/m2 (for 8 mol % yttria) to 1.27 ± 0.08 J/m2 (for 12 mol % yttria) for the hydrous surface and from 1.16 ± 0.08 J/m2 to 1.80 ± 0.10 J/m2 for the anhydrous surface. Interface enthalpies were determined to be in the range of 0.9 ± 0.5 J/m2 for all studied compositions. Comparisons with measured surface energies for pure ZrO2, and Y2O3 nanopowders and grain-boundary energies for YSZ dense nanoceramics are presented.
A new structure-from-motion ambiguity (2000)

Demonstrates the existence of an approximate, intrinsic ambiguity in Euclidean structure from motion (SFM) which occurs as generically as the bas-relief ambiguity but, unlike it, strengthens for scenes with more depth variation. The ambiguity does not occur in projective SFM, but the reasons for this make projective reconstructions more likely to have large errors. Our analysis gives a semiquantitative characterization of the least-squares error surface over a domain complementary to that analyzed by Jepson, Heeger, and Maybank. As part of our analysis, we show that the least-squares error for infinitesimal motion-the optical-flow error-gives a good approximation to the least-squares error for moderate finite motions. We propose that many high-error local minima occur for epipoles in or near the image. We also establish the existence of a new local minimum in minimizing over the rotation, given the translation direction.
Forced Expression of Murine IL-17E Induces Growth Retardation, Jaundice, a Th2-Biased Response, and Multiorgan Inflammation in Mice (2001)

IL-17 is a proinflammatory cytokine, and its in vivo expression induces neutrophilia in mice. IL-17E is a recently described member of an emerging family of IL-17-related cytokines. IL-17E has been shown to bind IL-17Rh1, a protein distantly related to the IL-17R, suggesting that IL-17E probably possesses unique biological functions. In this study, we have identified the murine ortholog of IL-17E and developed transgenic mice to characterize its actions in vivo. Biological consequences of overexpression of murine (m)IL-17E, both unique to IL-17E and similar to IL-17, were revealed. Exposure to mIL-17E resulted in a Th2-biased response, characterized by eosinophilia, increased serum IgE and IgG1, and a Th2 cytokine profile including elevated serum levels of IL-13 and IL-5 and elevated gene expression of IL-4, IL-5, IL-10, and IL-13 was observed in many tissues. Increased gene expression of IFN-gamma in several tissues and elevated serum TNF-alpha were also noted. In addition, IL-17E induces G-CSF production in vitro and mIL-17E-transgenic mice had increased serum G-CSF and exhibit neutrophilia, a property shared by IL-17. Moreover, exposure to mIL-17E elicited pathological changes in multiple tissues, particularly liver, heart, and lungs, characterized by mixed inflammatory cell infiltration, epithelial hyperplasia, and hypertrophy. Taken together, these findings suggest that IL-17E is a unique pleiotropic cytokine and may be an important mediator of inflammatory and immune responses.
Long-Term Outcome of RPE Allografts in Non-Immunosuppressed Patients with AMD (1999)

Subretinal human RPE allografts present a high rejection rate (75%) without immunosuppression. However, small extrafoveal transplants remained unchanged in shape, size and color for more than two years in non-exudative AMD. A disrupted BRB is likely to enhance graft rejection, which occurs earlier in exudative than in non-exudative AMD.
A Multi-Modality Assay Platform for Ultra-High Throughput Screening (2000)

The demand for increased throughput during primary screening using less reagents is changing the way of drug discovery. Searching for hits using high throughput screening in 96-well format plates is being replaced by the use of higher density plates, such as 384 and 1536-well formats. The analysis of radiometric assays by scintillation counters is becoming limiting since only 12 wells can be counted at a time. Charged coupled device (CCD) camera based instruments, that image the whole plate in one exposure, speed up detection and are compatible with any microplate footprint. Researchers are also demanding a choice of detection methods, including fluorescence, luminescence and radioactivity, and require imagers suitable for all applications. LEADseeker Homogenous Imaging System is a multi-modality platform offering imaging technology and assay toolboxes for radiometric, fluorescent and luminescent based assays. LEADseeker allows the very rapid analysis of high density formats enabling ultra-high throughput screening of a range of biological assays. Research areas that can be studied using this system include enzyme assays, receptor binding and molecular interactions.
Encapsidation of turnip crinkle virus is defined by a specific packaging signal and RNA size (1997)

A protoplast infection assay has been used to reliably examine the viral RNA encapsidation of turnip crinkle virus (TCV). Analysis of the encapsidation of various mutant viral RNAs revealed that a 186-nucleotide (nt) region at the 3' end of the coat protein (CP) gene, with a bulged hairpin loop of 28 nt as its most essential element, was indispensable for TCV RNA encapsidation. When RNA fragments containing the 186-nt region were used to replace the CP gene of a different virus, tomato bushy stunt virus, the resulting chimeric viral RNAs were encapsidated into TCV virions. Furthermore, analysis of the encapsidated chimeric RNA species established that the RNA size was an important determinant of the TCV assembly process.
A benign cultured colon adenoma bears three genetically altered colon cancer oncogenes, but progresses to tumorigenicity and transforming growth factor-beta independence without inactivating the p53 tumor suppressor gene. (1994)

We describe the spontaneous progression of a colon adenoma cell line to tumorigenicity and growth factor independence. This system allows direct comparison of biologic stages of malignant progression with alterations of colon cancer suppressor genes and oncogenes. VACO-235, a human colon adenoma cell line, is at early passages nontumorigenic in the nude mouse, unable to grow in soft agar, growth stimulated by serum and EGF, and growth inhibited by TGF-beta. VACO-235 daughter passages 93 and higher have in culture spontaneously progressed to being weakly tumorigenic, but retain all other growth characteristics of VACO-235 early passages. A mouse xenograft from late passage VACO-235 was reestablished in culture as the granddaughter cell line, VACO-411. VACO-411 is highly tumorigenic, clones in soft agar, and is unresponsive to serum, EGF, and TGF-beta. Early passage VACO-235 bears a mutant K-ras allele, bears only mutant APC alleles, expresses no DCC transcripts, and expresses only wild type p53 transcripts. VACO-411 retains the identical genotype, still expressing only wild type p53. Colonic cells after ras mutation, APC mutation, and DCC inactivation remain nontumorigenic and growth factor dependent. Malignant progression involves at least two additional steps, and in VACO-411 can proceed by a novel pathway not requiring p53 inactivation.
PIK3CA Gene Amplification and PI3K p110α Protein Expression in Breast Carcinoma (2014)

A family of PI3Ks is the lipid kinases, which enhance intracellular pools of phosphatidyl inositol 3,4,5-tri-phosphate (PIP3) through phosphorylating its precursor. Amplifications and deletions of genes, as well as somatic missense of the PIK3CA gene have been described in many human cancer varieties, including of the brain, colon, liver, lung and stomach. Immunohistochemistry and Real-time quantitative PCR tests were used to determine the PIK3CA gene amplification (gene copy number) and to detect protein expression, respectively. The results obtained were analysed and the ratio of PIK3CA to β-actin gene copy number was calculated. Positive gene amplification of PIK3CA was appointed as a copy number of ≥4. Also, PI3K p110α protein expression was scored from 0 to 3+ and the scores of 2+ and 3+ were considered as positive for PI3K p110α protein expression. We studied 50 breast carcinoma samples for PI3K p110α protein expression and PIK3CA gene copy numbers. In general, 36 out of 50 (72%) breast carcinoma samples showed a significant increase in PIK3CA gene amplification. 12 out of 50 (24%) showed positive staining, and 38 out of 50 (76%) showed negative staining for PI3K p110α expression. We have identified no significant relationship between PIK3CA amplification, race (p= 0.630) and histological type (p=0. 731) in breast carcinoma, but correlation of PIK3CA amplification and age showed a significant relationship (p=0. 003) between them. No significant relationship has been identified in correlation of PI3K p110α protein expression compared to age (p=0. 284), race (p=0. 546) and histological type (p=0. 285). Amplification of PIK3CA was frequent in breast carcinoma and occurs in stages of breast carcinoma. Our result shows that there is a relationship between gene amplification and age in breast carcinoma. We suggest that PIK3CA is significant in breast tumorigenesis serve as a prevalent mechanism contributes to the oncogenic activation pathway of PIK3CA in breast cancer.
A MIB for video server system management (2002)

A video server system provides many different types of interactive video services including: video on demand, home shopping, interactive games, etc. Both the use of the interactive video services and the video server itself need managing. This ranges from configuring the system, handling and logging faults, through monitoring the performance, etc. This paper describes how to structure the management information base (MIB) for managing DAVIC compliant video server systems. It is described in terms of the management protocol developed by Internet Engineering Task Force (IETF) known as the Simple Network Management Protocol (SNMP).
Synthesis of Nickel−Nitrilotriacetic Acid Coupled Single-Walled Carbon Nanotubes for Directed Self-Assembly with Polyhistidine-Tagged Proteins (2008)

Nickel−nitrilotriacetic acid-functionalized single-walled carbon nanotubes have been synthesized for the directed, reversible self-assembly of polyhistidine-tagged macromolecules onto the nanotube surface. Carbon nanotubes were first covalently functionalized with 4-carboxybenzene diazonium salt, which rendered them water-soluble. The acid moieties on the carbon nanotube were covalently reacted with Nα,Nα-bis(carboxymethyl)-l-lysine hydrate, forming amide bonds to the nanotube complex. The nitrilotriacetic acid (NTA) moiety of the Nα,Nα-bis(carboxymethyl)-l-lysine was complexed with Ni2+ and used to specifically bind a polyhistidine-tagged photosynthetic reaction center (RC) from Rhodobacter sphaeroides as a model system. We demonstrate that the histidine-tagged RC protein (RC-His) specifically binds to SWNT-NTA-Ni in a reversible manner. The free RC-His in solution can be removed through histidine binding to Ni-NTA-agarose resin and purified by filtration. This approach allows for both positional and orientational control over protein binding to carbon nanotubes.
Gatekeeper Mutations Mediate Resistance to BRAF-Targeted Therapies (2010)

BRAF is a serine-threonine-specific protein kinase that is mutated in 2% of human cancers. Oncogenic BRAF is a validated therapeutic target that constitutively activates mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling, driving tumor cell proliferation and survival. Drugs designed to target BRAF have been developed, but it is difficult to prove that they mediate their antitumor effects by inhibiting BRAF rather than by working through off-target effects. We generated drug-resistant versions of oncogenic BRAF by mutating the gatekeeper residue. Signaling by the mutant proteins was resistant to the small-molecule inhibitor sorafenib, but sorafenib still inhibited the growth of tumors driven by the mutant protein. In contrast, both BRAF signaling and tumor growth were resistant to another RAF drug, PLX4720. These data provide unequivocal evidence that sorafenib mediates its antitumor effects in a manner that is independent of its ability to target oncogenic BRAF, whereas PLX4720 inhibits tumor growth by targeting oncogenic BRAF directly.
Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation (2008)

Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine. To elucidate the molecular mechanism by which leucine stimulates protein synthesis in neonatal muscle, overnight-fasted 7-day-old piglets were treated with rapamycin [an inhibitor of mammalian target of rapamycin (mTOR) complex (mTORC)1] for 1 h and then infused with leucine for 1 h. Fractional rates of protein synthesis and activation of signaling components that lead to mRNA translation were determined in skeletal muscle. Rapamycin completely blocked leucine-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Rapamycin blocked the leucine-induced phosphorylation of mTOR, S6 kinase 1 (S6K1), and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1) and formation of the eIF4E.eIF4G complex and increased eIF4E.4E-BP1 complex abundance. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation, or G protein beta-subunit-like protein (GbetaL), a component of mTORC1 and mTORC2. Neither leucine nor rapamycin affected the phosphorylation of AMP-activated protein kinase (AMPK), PKB, or tuberous sclerosis complex (TSC)2, signaling components that reside upstream of mTOR. Eukaryotic elongation factor (eEF)2 phosphorylation was not affected by leucine or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR dependent. Together, these in vivo data suggest that leucine stimulates muscle protein synthesis in neonates by enhancing mTORC1 activation and its downstream effectors.
Muscarinic Receptor Subtypes in Smooth Muscle (2020)

Muscarinic Receptor Classification, M. Caulfield Muscarinic Acetylcholine Receptor Signaling Pathways in Smooth Muscle, R.A.J. Challiss and J.L. Blank Muscarinic Receptors and Gastrointestinal Smooth Muscle, F.J. Ehlert, E.A. Thomas, E.H. Gerstin, and M.T. Griffin Muscarinic Receptors and Genitourinary Smooth Muscle, R.M. Eglen and S.S. Hegde Prejunctional Muscarinic Receptors and Smooth Muscle, N. Watson Index