gebhart/patrepeval huggingface dataset:
Notch Signaling Determines the M1 versus M2 Polarization of Macrophages in Antitumor Immune Responses (2010)

Macrophages are important tumor-infiltrating cells and play pivotal roles in tumor growth and metastasis. Macrophages participate in immune responses to tumors in a polarized manner: classic M1 macrophages produce interleukin (IL) 12 to promote tumoricidal responses, whereas M2 macrophages produce IL10 and help tumor progression. The mechanisms governing macrophage polarization are unclear. Here, we show that the M2-like tumor-associated macrophages (TAM) have a lower level of Notch pathway activation in mouse tumor models. Forced activation of Notch signaling increased M1 macrophages which produce IL12, no matter whether M1 or M2 inducers were applied. When Notch signaling was blocked, the M1 inducers induced M2 response in the expense of M1. Macrophages deficient in canonical Notch signaling showed TAM phenotypes. Forced activation of Notch signaling in macrophages enhanced their antitumor capacity. We further show that RBP-J-mediated Notch signaling regulates the M1 versus M2 polarization through SOCS3. Therefore, Notch signaling plays critical roles in the determination of M1 versus M2 polarization of macrophages, and compromised Notch pathway activation will lead to the M2-like TAMs. These results provide new insights into the molecular mechanisms of macrophage polarization and shed light on new therapies for cancers through the modulation of macrophage polarization through the Notch signaling.
p‐Toluenesulfonyl Chloride as an Activating Agent of Agarose for the Preparation of Immobilized Affinity Ligands and Proteins (1980)

A number of biomolecules were coupled covalently by nucleophilic displacement to agarose preparations substituted with tosyl groups. In one series of experiments N6-(6-aminohexyl)-adenosine 5'-monophosphate and N6-(6-aminohexyl)adenosine 2',5'-bisphosphate were bound by their terminal amino groups to the polysaccharide support. It could be shown that from a mixture of lactate and 6-phosphogluconate dehydrogenase the immobilized monophosphate showed bio-affinity only for NAD+-dependent lactate dehydrogenase, whereas the immobilized bisphosphate showed affinity only for the NADP+-dependent 6-phosphogluconate dehydrogenase. Furthermore, the immobilized monophosphate (5 mumol/g wet gel) was applied for the single-step purification of lactate dehydrogenase from crude beef heart extract. To demonstrate the immobilization of proteins, soybean trypsin inhibitor (75 mg/g dry support) was immobilized to tosylated agarose, tested as affinity chromatography material and shown to bind 60 mg trypsin/g dry gel. Horseradish peroxidase and horse liver alcohol dehydrogenase were used as model enzymes. Although no optimization had been attempted, the former (approximately 70 mg/g dry support) had a coupling yield of approximately 18% with a specific activity (relative to soluble enzyme) of approximately 10%, whereas approximately 60% of alcohol dehydrogenase was coupled (approximately 100 mg/g dry support) with a specific activity of approximately 25%.
Conformational Stability of Proteins (1993)

The stability of a protein, i.e., its usefulness as a biologically active molecule, depends on the particular environment and the exposure to conditions that can promote chemical deterioration or conformational changes.
Supporting medical conversations between deaf and hearing individuals with tabletop displays (2008)

This paper describes the design and evaluation of Shared Speech Interface (SSI), an application for an interactive multitouch tabletop display designed to facilitate medical conversations between a deaf patient and a hearing, non-signing physician. We employ a participatory design process involving members of the deaf community as well as medical and communication experts. We report results from an evaluation that compares conversation when facilitated by: (1) a digital table, (2) a human sign language interpreter, and (3) both a digital table and an interpreter. Our research reveals that tabletop displays have valuable properties for facilitating discussion between deaf and hearing individuals as well as enhancing privacy and independence. The contributions of this work include initial guidelines for cooperative group work technology for users with varying hearing abilities, discussion of benefits of participatory design with the deaf community, and lessons about using dictated speech on shared displays.
Rock Cutting By Laser (1971)

Introduction A recent study of laser-assisted mechanical rock tunneling, conducted at the United Aircraft Research Laboratories under Department of Transportation sponsorship, had as a goal the investigation of laser-assisted mechanical rock fracture for use in tunneling machines boring in extremely hard rock. The results of this study, which are reported in Ref. 1, indicate that the use of the laser in a low-power-density mode to preweaken the rock without causing malting of the rock surface is indeed a feasible mode of weakening hard rock, which does allow a reduction in the energy required for subsequent mechanical removal of the rock. However the system studies undertaken in Ref. 1 indicate that the amount of strength reduction achieved by the laser or any other type of heating system would not be sufficient to justify economically the addition of an expensive heating system to a hard rock tunneling machine. One avenue toward employing concentrated heat energy which appears to have a potentially greater efficiency in reducing potentially greater efficiency in reducing the strength of hard rock was identified in the Ref. 1 study. This concept involves using highly concentrated thermal energy to form very narrow melt cuts in the rock. This mode of rock weakening has two advantages relative to the use of the low-power-density heating mode in which rock melting is not allowed to occur. For one thing, the use of an extremely high-power-density energy beam allows penetration of the heat into the rock at substantially higher speeds than the nonmelting case, in which penetration speeds are based on the speed of thermal diffusion into the solid rock. Secondly, there are indications that the deposition of heat at depth in the rock could allow removal of a much greater rock volume than the same amount of heat if it were allowed simply to heat-weaken an entire surface area. Careful use of a very highly concentrated heat tool could allow weakening of rock along specific planes, with subsequent removal of relatively large pieces of rock bounded by these planes.
Endothelial monolayer permeability to macromolecules. (1987)

The barrier function of the endothelial monolayer has not been extensively investigated using the cultured endothelium. The in vitro approach may contribute to a more complete understanding of microvessel wall permeability. Our studies using an in vitro endothelial monolayer system have led us to the following conclusions: the endothelial monolayer is more permeable to small-molecular-weight substances than to large molecules; the permeability of albumin is different for endothelial cells derived from different vascular sites (higher for pulmonary venous than pulmonary arterial endothelium); basement membrane components may have a significant role in the permeability of albumin across the endothelium; control of endothelial monolayer permeability is determined not only by the characteristics of the macromolecule (i.e., size and charge) but also by the shape of the endothelial cells and the size of interendothelial space.
Exchange rates of creatine kinase metabolites: feasibility of imaging creatine by chemical exchange saturation transfer MRI (2012)

Creatine (Cr), phosphocreatine (PCr) and adenosine-5-triphosphate (ATP) are major metabolites of the enzyme creatine kinase (CK). The exchange rate of amine protons of CK metabolites at physiological conditions has been limited. In the current study, the exchange rate and logarithmic dissociation constant (pKa) of amine protons of CK metabolites were calculated. Further, the chemical exchange saturation transfer effect (CEST) of amine protons of CK metabolites with bulk water was explored. At physiological temperature and pH, the exchange rate of amine protons in Cr was found to be 7-8 times higher than PCr and ATP. A higher exchange rate in Cr was associated with lower pKa value, suggesting faster dissociation of its amine protons compared to PCr and ATP. CEST MR imaging of these metabolites in vitro in phantoms displayed predominant CEST contrast from Cr and negligible contribution from PCr and ATP with the saturation pulse parameters used in the current study. These results provide a new method to perform high-resolution proton imaging of Cr without contamination from PCr. Potential applications of these finding are discussed.
Aging, proteotoxicity, mitochondria, glycation, NAD+ and carnosine: possible inter-relationships and resolution of the oxygen paradox (2010)

It is suggested that NAD(+) availability strongly affects cellular aging and organism lifespan: low NAD(+) availability increases intracellular levels of glycolytic triose phosphates (glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate) which, if not further metabolized, decompose spontaneously into methylglyoxal (MG), a glycating agent and source of protein and mitochondrial dysfunction and reactive oxygen species (ROS). MG-damaged proteins and other aberrant polypeptides can induce ROS generation, promote mitochondrial dysfunction and inhibit proteasomal activity. Upregulation of mitogenesis and mitochondrial activity by increased aerobic exercise, or dietary manipulation, helps to maintain NAD(+)availability and thereby decreases MG-induced proteotoxicity. These proposals can explain the apparent paradox whereby aging is seemingly caused by increased ROS-mediated macromolecular damage but is ameliorated by increased aerobic activity. It is also suggested that increasing mitochondrial activity decreases ROS generation, while excess numbers of inactive mitochondria are deleterious due to increased ROS generation. The muscle- and brain-associated dipeptide, carnosine, is an intracellular buffer which can delay senescence in cultured human fibroblasts and delay aging in senescence-accelerated mice. Carnosine's ability to react with MG and possibly other deleterious carbonyl compounds, and scavenge various ROS, may account for its protective ability towards ischemia and ageing.
Epitaxial growth of TiN films on (100) silicon substrates by laser physical vapor deposition (1992)

We report epitaxial growth of TiN films having low resistivity on (100) silicon substrates using pulsed laser deposition method. The TiN films were characterized using x-ray diffraction, Rutherford backscattering, four-point-probe ac resistivity, high resolution transmission electron microscopy and scanning electron microscopy techniques and epitaxial relationship was found to be 〈100〉 TiN ∥ 〈100〉 Si. TiN films showed 10%–20% channeling yield. In the plane, four unit cells of TiN match with three unit cells of silicon with less than 4.0% misfit. This domain matching epitaxy provides a new mechanism of epitaxial growth in systems with large lattice misfits. Four-point-probe measurements show characteristic metallic behavior of these films as a function of temperature with a typical resistivity of about 15 μΩ cm at room temperature. Implications of low-resistivity epitaxial TiN in silicon device fabrication are discussed.
Security verification of hardware-enabled attestation protocols (2012)

Hardware-software security architectures can significantly improve the security provided to computer users. However, we are lacking a security verification methodology that can provide design-time verification of the security properties provided by such architectures. While verification of an entire hardware-software security architecture is very difficult today, this paper proposes a methodology for verifying essential aspects of the architecture. We use attestation protocols proposed by different hardware security architectures as examples of such essential aspects. Attestation is an important and interesting new requirement for having trust in a remote computer, e.g., in a cloud computing scenario. We use a finite-state model checker to model the system and the attackers, and check the security of the protocols against attacks. We provide new actionable heuristics for designing invariants that are validated by the model checker and thus used to detect potential attacks. The verification ensures that the invariants hold and the protocol is secure. Otherwise, the protocol design is updated on a failure and the verification is re-run.
Technology for Oral Assessment (2008)

With recent developments in multimedia recording, researchers have begun to investigate the use of technology in oral proficiency assessment. This article addresses the benefits and ease of using seven different multimedia tools to assess P-16 students’ oral language proficiency and compares traditional methods of in-class oral language assessment to out-of-class recordings. Additionally, the authors discuss the potential benefits of using technology to lower students’ affective filter, to provide teachers with a digital portfolio of student progress, and to increase instructional and preparation time.
Molecular mechanisms involved in gamete interaction: evidence for the participation of cysteine-rich secretory proteins (CRISP) in sperm-egg fusion. (2007)

Epididymal protein DE and testicular protein Tpx-1 are two cysteine-rich secretory proteins also known as CRISP-1 and CRISP-2, respectively. DE/ CRISP-1 is localised on the equatorial segment of acrosome-reacted sperm and participates in rat gamete fusion through its binding to egg-complementary sites. Recent results using bacterially-expressed recombinant fragments of DE as well as synthetic peptides revealed that the ability of DE to bind to the egg surface and inhibit gamete fusion resides in a region of 12 amino acids corresponding to an evolutionary conserved motif of the CRISP family (Signature 2). Given the high degree of homology between DE/CRISP-1 and Tpx-1/CRISP-2, we also explored the potential participation of the testicular intra-acrosomal protein in gamete fusion. Results showing the ability of recombinant Tpx-1 to bind to the surface of rat eggs (evaluated by indirect immunofluorescence) and to significantly inhibit zona-free egg penetration, support the participation of this protein in gamete fusion through its interaction with egg-binding sites. Interestingly, rat Tpx-1 exhibits only two substitutions in Signature 2 when compared to this region in DE. Together, these results provide evidence for the involvement of both epididymal DE/CRISP-1 and testicular Tpx-1/CRISP-2 in gamete fusion suggesting the existence of a functional cooperation between homologue molecules as a mechanism to ensure the success of fertilisation.
A New Calculus for the Treatment of Optical SystemsVI Experimental Determination of the Matrix* (1947)

A simple, straightforward method is described for determining experimentally the matrix of any, crystalline plate. The method involves three measurements of the state of polarization of light transmitted by the plate, and also a measurement of its transmission factor for natural light. These measurements determine the matrix uniquely, except for a phase factor whose practical significance is small. The conditions are stated for the application of the method to the more general type of optical system described in V. A statement of the content of future papers in this series is included.
Monoclonal antibody against the common beta subunit (beta c) of the human interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony- stimulating factor receptors shows upregulation of beta c by IL-1 and tumor necrosis factor-alpha (1992)

High-affinity receptors for human granulocyte macrophage colony- stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are composed of two distinct subunits, alpha and beta. Each receptor has its own ligand-specific alpha subunit, and the three receptors share the common beta subunit, beta c. Using a transfectant of NIH3T3 cells expressing the high-affinity human GM-CSF receptor, monoclonal antibodies (MoAbs) against beta c were generated. These MoAbs specifically bound to cells bearing beta c and immunoprecipitated the beta c protein of 120 Kd. Using these MoAbs, expression of beta c was examined. It is known that IL-1 augments the proliferative response of a human factor-dependent hematopoietic cell line TF-1 to either GM-CSF, IL-3, or IL-5, and that it upregulates the high-affinity receptors for GM-CSF, IL-3, and IL-5. Antibody binding and immunoprecipitation demonstrated that IL-1 increased cell surface expression of beta c. This enhancement by IL-1 was accompanied by an increased level of beta c mRNA. In addition, we found that tumor necrosis factor-alpha (TNF- alpha) also increased the expression of beta c, although it did not augment the proliferative response of TF-1 to GM-CSF, IL-3, and IL-5.
Macrophages: Central regulators of hepatic fibrogenesis and fibrosis resolution (2012)

Hepatic fibrosis is the common end point to chronic injury of varied aetiology. There is now excellent evidence in both human studies and animal models that liver fibrosis is a bidirectional process with a significant reversible component. The hepatic stellate cell (HSC), following activation to a myofibroblast phenotype, is the principal cell producing extracellular matrix (ECM) during fibrogenesis and is the main source of TIMP-1, which inhibits the endogenous matrix-degrading activity of matrix metalloproteinases (MMPs), thus promoting scar deposition. Furthermore, apoptosis of activated HSCs is a critical feature of scar resolution. However, emerging evidence indicates that it is the hepatic macrophage that is the master regulator of this dynamic fibrogenesis–fibrosis resolution paradigm.
Stress reduction and analgesia in patients exposed to calming music postoperatively (2005)

This study suggests that intraoperative music may decrease postoperative pain, and that postoperative music therapy may reduce anxiety, pain and morphine consumption.
Role of Unique Consecutive Glutamine Repeats in Active Murine Interleukin-2 Molecule (1987)

Murine interleukin-2 (MIL-2) cDNA deleted of 11 repeats of a CAG sequence, and that encoded from 33Met to 149Gln were inserted into an expression vector carrying an Escherichia coli tryptophan promoter and were expressed in E. coli, respectively. Recombinant MIL-2 deleted of 11 glutamine repeats (MIL-2(-Gln] supported the growth of murine CTLL-2 cells but recombinant MIL-2 initiated from 34Asp (34Asp-MIL-2) did not. The growth of human T-cell blasts was not supported by MIL-2(-Gln) or 34Asp-MIL-2. MIL-2(-Gln) had identical biological and immunological activities with intact MIL-2, but 34Asp-MIL-2 did not. These results suggest that the consecutive glutamine repeats do not play a role in the biological and immunological activities of MIL-2, but that the peptide sequence around them does, and the species hierarchy that MIL-2 does not act on human lymphocyte is not due to the presence of glutamine repeats in MIL-2.
Down-Regulation of microRNA-26a Promotes Mouse Hepatocyte Proliferation during Liver Regeneration (2012)

MiR-26a plays crucial role in regulating the proliferative phase of LR, probably by repressing expressions of cell cycle proteins CCND2 and CCNE2. The current study reveals a novel miRNA-mediated regulation pattern during the proliferative phase of LR.
Poststreptococcal reactive arthritis (2000)

The occurrence of an entity designated poststreptococcal reactive arthritis (PSReA) has been highlighted in recent reports. The syndrome was considered part of the spectrum of acute rheumatic fever by some, whereas others stressed the differences between the two diseases. As distinct from acute rheumatic fever, PSReA is characterized by a shorter latency period between the inciting streptococcal infection and the onset of arthritis, a higher frequency of involvement of the small joints and axial skeleton, poor response to aspirin and other nonsteroidal anti-inflammatory drugs, a protracted course of arthritis, a low incidence of carditis, and absence of other major manifestations of acute rheumatic fever. Recent studies have demonstrated an increased frequency of DRB1*01 in patients with PSReA, which contrasts with the increased frequency of DRB1*16 in rheumatic fever. Because 6% of patients with PSReA have been reported to have late onset carditis, it is judicious to recommend that patients with PSReA receive prophylactic antimicrobials for a minimum period of 5 years or until the age of 21 years, whichever is longer.
Extending Insulin Action in Vivo by Conjugation to Carboxymethyl Dextran (1998)

The biochemical and pharmacological properties of bioactive peptides and proteins can be altered by conjugation with polymers. This report describes site-specific attachment of insulin to activated carboxyl groups of carboxymethyl dextran (CMD, MW=51000) through the GlyA1 insulin amino group. On average, three or four insulin molecules were grafted to a CMD linear chain. Coupled insulin molecules were properly folded, and the bioactivity of conjugated insulin in the blood glucose depression assay was 9.6 IU/mg, which was only 2.6 times less than that for native insulin. The cell growth study indicated that the CMD-insulin conjugate was as mitogenic as insulin on vascular smooth muscle cells, whereas the starting CMD polymer was not. The insulin receptor binding constant of the conjugate (3.6 x 10[9] M[-1]) compared well with that of native insulin (7.6 x 10[9] M[-1]), indicating that the CMD chain does not present any major constraints to binding. Plasma clearance of CMD-insulin obeyed a two-compartment pharmacokinetic (PK) model with a CMD-insulin conjugate plasma elimination half-life of 114.1 min, which was significantly longer than that of soluble Zn-insulin (12.4 min). In contrast, pharmacodynamic (PD) profiles (blood glucose lowering effects) after intravenous (iv) administration of the conjugate or insulin in rats were not different. Subcutaneous (sc) administration of the conjugate resulted in a significantly prolonged plasma profile with a noncompartmental PK parameter mean residence time (MRT) of 103.5 min which was significantly longer than that of soluble Zn-insulin (40.5 min). This was reflected in the protracted PD effect of sc administered conjugate with time needed to reach minimum glucose concentration Tnadir of 95.7 min, which was significantly longer than that of insulin (62 min). We conclude that the conjugation of insulin to CMD leads to a bioactive conjugate with a delayed sc PD profile showing prolonged response, resembling intermediate acting insulin preparations.
A Novel Sulfonylurea Receptor Forms with BIR (Kir6.2) a Smooth Muscle Type ATP-sensitive K+ Channel (1996)

We have isolated a cDNA encoding a novel isoform of the sulfonylurea receptor from a mouse heart cDNA library. Coexpression of this isoform and BIR (Kir6.2) in a mammalian cell line elicited ATP-sensitive K+ (KATP) channel currents. The channel was effectively activated by both diazoxide and pinacidil, which is the feature of smooth muscle KATP channels. Sequence analysis indicated that this clone is a variant of cardiac type sulfonylurea receptor (SUR2). The 42 amino acid residues located in the carboxyl-terminal end of this novel sulfonylurea receptor is, however, divergent from that of SUR2 but highly homologous to that of the pancreatic one (SUR1). Therefore, this short part of the carboxyl terminus may be important for diazoxide activation of KATP channels. The reverse transcription-polymerase chain reaction analysis showed that mRNA of this clone was ubiquitously expressed in diverse tissues, including brain, heart, liver, urinary bladder, and skeletal muscle. These results suggest that this novel isoform of sulfonylurea receptor is a subunit reconstituting the smooth muscle KATP channel.