gebhart/patrepeval huggingface dataset:
Integrin-linked kinase and PINCH: partners in regulation of cell-extracellular matrix interaction and signal transduction (1999)

Integrin-linked kinase (ILK) is a focal adhesion serine/threonine protein kinase that is emerging as a key signaling protein functioning at one of the early convergence points of integrin- and growth factor-signaling pathways. ILK binds to PINCH through the N-terminal ankyrin (ANK) repeat domain and the PINCH binding is crucial for focal adhesion localization of ILK. The ILK-PINCH interaction also connects ILK to Nck-2, an SH2-SH3-containing adaptor protein that interacts with components of growth factor and small GTPase signaling pathways. The kinase activity of ILK is regulated by both cell adhesion and growth factors in a phosphoinositide 3-kinase (PI3K)-dependent manner. ILK phosphorylates downstream targets such as protein kinase B (PKB, also known as Akt) and glycogen synthase kinase 3 (GSK-3) and regulates their activities. Overexpression of ILK in epithelial cells leads to striking morphological changes mimicking epithelial-mesenchymal transition, including upregulation of integrin-mediated fibronectin matrix assembly and downregulation of cell-cell adhesions. Furthermore, ILK regulates nuclear translocation of (beta)-catenin and gene expression, and promotes cell cycle progression and tumor formation. Recent genetic studies in Drosophila melanogaster and Caenorhabditis elegans have shown that lack of expression of ILK or PINCH results in phenotypes resembling those of integrin-null mutants, which demonstrates that ILK and PINCH are indispensable for integrin function during embryonic development.
<title>Airborne chemical contamination of a chemically amplified resist</title> (1991)

We have found that the performance of the t-BOC/onium salt resist system is severely degraded by vapor from organic bases. This effect is very pronounced and can be observed when the coated wafers stand for 15 minutes in air containing as little as 15 parts per billion (ppb) of an organic base. The observed effect, caused by this chemical contamination, depends on the tone of the resist system. For negative tone systems the UV exposure dose, required to obtain the correct linewidth, increases. While for the positive tone system, one observes the generation of a skin at the resist-air interface. Both effects are caused by the photogenerated acid being neutralized by the airborne organic base. There are a wide variety of commonly used materials which can liberate trace amounts of volatile amines and degrade resist performance. For example, fresh paint on a laboratory wall can exhibit this detrimental effect. These effects can be minimized by storing and processing the resist coated wafers in air that has passed through a specially designed, high efficiency carbon filter. The implementation of localized air filtration, to bathe the resist in chemically pure air, enabled this resist system to operate in a manufacturing environment at a rate of 100 wafers/hour.
Native Oxide Layers Formed on the Surface of Ultra High-Purity Iron and Copper Investigated by Angle Resolved XPS (1997)

Angle resolved X-ray photoelectron spectroscopy (AR-XPS) has been used for characterizing native oxide layers formed on the surface of ultra high-purity iron and copper by exposure to air at room temperature. Thickness of an oxide layer formed on the surface of ultra high-purity iron is found to be thicker than that for ultra high-purity copper in the initial stage of oxidation and almost unchanged by air exposure time. On the other hand, thickness of an oxide layer formed on ultra high-purity copper is found to increase with increasing air exposure time. These results are consistent with spectral information for ultra high-purity iron and copper exposed to air; the chemical state of Fe in the surface of ultra high-purity iron is almost independent of exposure time, whereas the chemical state varies in the surface of ultra high-purity copper by exposure for a long term.
Stereocontrolled General Synthesis of Pyrimidine C-Nucleosides Having Branched-chain Sugar Moieties (1983)

Abstract A variety of pyrimidine C-nucleosides bearing branched-chain sugars can be synthesized starting from adequately substituted (1R*,6S*,7S*,8R*)-7,8-isopropylidenedioxy-3,9-dioxabicyclo[4.2.1]nonan-4-ones. The general procedure consists of condensation with t-butoxybis(dimethylamino) methane, giving the corresponding α-dimethylaminomethylene lactones, base-catalyzed heterocycle formation with urea, thiourea, or guanidine, and acid-promoted removal of the isopropylidene protective group. The overall transformation proceeds with retention of the stereochemistry to afford only C-β-glycosyl nucleoside structures.
Suppressive effects of tumor cell-derived 5′-deoxy-5′-methylthioadenosine on human T cells (2016)

The immunosuppressive tumor microenvironment represents one of the main obstacles for immunotherapy of cancer. The tumor milieu is among others shaped by tumor metabolites such as 5'-deoxy-5'-methylthioadenosine (MTA). Increased intratumoral MTA levels result from a lack of the MTA-catabolizing enzyme methylthioadenosine phosphorylase (MTAP) in tumor cells and are found in various tumor entities. Here, we demonstrate that MTA suppresses proliferation, activation, differentiation, and effector function of antigen-specific T cells without eliciting cell death. Conversely, if MTA is added to highly activated T cells, MTA exerts cytotoxic effects on T cells. We identified the Akt pathway, a critical signal pathway for T cell activation, as a target of MTA, while, for example, p38 remained unaffected. Next, we provide evidence that MTA exerts its immunosuppressive effects by interfering with protein methylation in T cells. To confirm the relevance of the suppressive effects of exogenously added MTA on human T cells, we used an MTAP-deficient tumor cell-line that was stably transfected with the MTAP-coding sequence. We observed that T cells stimulated with MTAP-transfected tumor cells revealed a higher proliferative capacity compared to T cells stimulated with Mock-transfected cells. In conclusion, our findings reveal a novel immune evasion strategy of human tumor cells that could be of interest for therapeutic targeting.
Synthesis of decahydrocyclopentacyclo-octene derivatives via intramolecular photocycloaddition of Δα,β-butenolides and reductive cleavage (1980)

Irradiation of Δαβ-butenolides bearing but-3-enyl and penta-3,4-dienyl side-chains in the γ-position, (2) and (3), effected intramolecular [2 + 2] cycloaddition to form fused tricyclic lactones (4) and (5), respectively, as major products; reductive ring opening of the derived keto-acid (7a) and keto-ester (9) gave the octa- and deca-hydrocyclopentacyclo-octene derivatives (8) and (10) respectively.
Access granted: The imperative of innovation and standardization in information security (2007)

The management of digital identities, despite its potential to generate business value, creates significant engineering challenges for modern firms. In this paper, we first provide an architectural overview of identity and access management (IDAM) technologies along with an analysis of patenting activities to establish that the IDAM market segment dominates the information security sector. An empirical study, based on data pertaining to public firms with a significant share of the IDAM market, shows that regulations and the frequency of malicious attacks are strongly correlated with increasing demand. While demand for identity and access management products has been exponentially increasing, innovation has only been moving at a moderate rate after declining near the end of the market bubble of 2000. The stock market's valuation of IDAM firms, while controlling for overall market conditions, has consequently been fairly static since 2001 and has followed similar trends in other segments of the IT industry. We therefore propose a two-pronged strategy involving: (i) standardization efforts on the engineering front; and (ii) additional regulations to stimulate innovation by IDAM firms.
A Role for AQP5 in Activation of TRPV4 by Hypotonicity (2006)

Regulation of cell volume in response to changes in osmolarity is critical for cell function and survival. However, the molecular basis of osmosensation and regulation of cell volume are not clearly understood. We have examined the mechanism of regulatory volume decrease (RVD) in salivary gland cells and report a novel association between osmosensing TRPV4 (transient receptor potential vanalloid 4) and AQP5 (aquaporin 5), which is required for regulating water permeability and cell volume. Exposure of salivary gland cells and acini to hypotonicity elicited an increase in cell volume and activation of RVD. Hypotonicity also activated Ca2+ entry, which was required for subsequent RVD. Ca2+ entry was associated with a distinct nonselective cation current that was activated by 4alphaPDD and inhibited by ruthenium red, suggesting involvement of TRPV4. Consistent with this, endogenous TRPV4 was detected in cells and in the apical region of acini along AQP5. Importantly, acinar cells from mice lacking either TRPV4 or AQP5 displayed greatly reduced Ca2+ entry and loss of RVD in response to hypotonicity, although the extent of cell swelling was similar. Expression of N terminus-deleted AQP5 suppressed TRPV4 activation and RVD but not cell swelling. Furthermore, hypotonicity increased the association and surface expression of AQP5 and TRPV4. Both these effects and RVD were reduced by actin depolymerization. These data demonstrate that (i) activation of TRPV4 by hypotonicity depends on AQP5, not on cell swelling per se, and (ii) TRPV4 and AQP5 concertedly control regulatory volume decrease. These data suggest a potentially important role for TRPV4 in salivary gland function.
International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function. (1998)

This article does not aim to review in detail the properties of γ-aminobutyric acidA(GABAA)breceptors, because recent accounts of that topic are available. In this same journal, a review of the binding properties and pharmacology of these receptors has been published ([Sieghart, 1995][1]). Other
Determination of complex dielectric functions of ion implanted and implanted-annealed amorphous silicon by spectroscopic ellipsometry (1992)

Measuring with a spectroscopic ellipsometer (SE) in the 1.8–4.5 eV photon energy region we determined the complex dielectric function (ε = ε1 + iε2) of different kinds of amorphous silicon prepared by self-implantation and thermal relaxation (500 °C, 3 h). These measurements show that the complex dielectric function (and thus the complex refractive index) of implanted a-Si (i-a-Si) differs from that of relaxed (annealed) a-Si (r-a-Si). Moreover, its ε differs from the ε of evaporated a-Si (e-a-Si) found in the handbooks as ε for a-Si. If we use this ε to evaluate SE measurements of ion implanted silicon then the fit is very poor. We deduced the optical band gap of these materials using the Davis–Mott plot based on the relation: (ε2E2)1/3 ∼ (E− Eg). The results are: 0.85 eV (i-a-Si), 1.12 eV (e-a-Si), 1.30 eV (r-a-Si). We attribute the optical change to annihilation of point defects.
A 3D active microwave imaging system for breast cancer screening (2008)

&lt;p&gt;A 3D microwave imaging system suitable for clinical trials has been developed. The anatomy, histology, and pathology of breast cancer were all carefully considered in the development of this system. The central component of this system is a breast imaging chamber with an integrated 3D antenna array containing 36 custom designed bowtie patch antennas that radiate efficiently into human breast tissue. 3D full-wave finite element method models of this imaging chamber, complete with full antenna geometry, have been developed using Ansoft HFSS and verified experimentally. In addition, an electronic switching system using Gallium Arsenide (GaAs) absorptive RF multiplexer chips, a custom hardware control system with a parallel port interface utilizing TTL logic, and a custom software package with graphical user interface using Java and LabVIEW have all been developed. Finally, modeling of the breast (both healthy and malignant) was done using published data of the dielectric properties of human tissue, confirming the feasibility of cancer detection using this system.&lt;/p&gt;
New tyrosine kinase inhibitors in chronic myeloid leukemia. (2005)

The deregulated activity of BCR-ABL tyrosine kinase originating from the t(9;22) chromosomal translocation has been shown to be necessary and sufficient for the transformed phenotype of chronic myeloid leukemia (CML) cells. This peculiarity has paved the way for the development of novel therapies specifically targeting the BCR-ABL gene product. The first BCR-ABL inhibitor to come into use in clinical practice, imatinib mesylate, is now the first-choice treatment for all newly diagnosed CML patients, but the initial striking efficacy of this drug has been overshadowed by the development of clinical resistance. The most common mechanisms of resistance include (i) BCR-ABL overexpression, and (ii) BCR-ABL kinase domain mutations disrupting critical contact points between imatinib and BCR-ABL or inducing a transition to a conformation to which imatinib is unable to bind. Several approaches to overcoming resistance have been studied both in vitro and in vivo. They include dose escalation of imatinib, the combination of imatinib with chemotherapeutic drugs, alternative BCR-ABL inhibitors, and inhibitors of kinases acting downstream of BCR-ABL such as Src kinases. Various novel tyrosine kinase inhibitors (TKI) have been synthesized and have now reached the pre-clinical or clinical phase. This review highlights the development of new TKI as specific molecularly targeted therapy and as the principal mechanisms for overcoming imatinib resistance.
Monoclonal antibodies specific for Semliki Forest virus replicase protein nsP2. (1997)

A panel of monoclonal antibodies (MAbs) was raised against Semliki Forest virus (SFV) nonstructural protein nsP2, which is a protease, an NTPase, a putative RNA helicase, and a regulator of the synthesis of the subgenomic 26S mRNA encoding the structural proteins. nsP2, used for immunization, was expressed as a histidine fusion protein in Escherichia coli and purified by metal affinity chromatography. Dot-blot assay, using a membrane fraction from SFV-infected cells as antigen, gave 33 positive clones. Of these, 30 MAbs recognized nsP2 in Western immunoblotting, and 25 showed positive indirect immunofluorescence (IFAT) in SFV-infected cells; 15 MAbs stained the cytoplasmic vacuoles (CPVI), which are the sites of viral RNA synthesis in alphavirus-infected cells. MAb 3B5 recognized only CPVIs, as shown by double immunofluorescence staining with polyclonal anti-nsP3 antiserum. Most of the MAbs (20/33) recognized the nuclear form of nsP2, which may be associated with SFV neurovirulence. Immunoprecipitation with MAbs revealed that the SFV nonstructural proteins are associated with each other. None of the MAbs recognized Sindbis virus nsP2 in immunoblotting, indicating that they were directed to non-conserved sequences specific for SFV. Interestingly, these epitopes were located mostly within the N-terminal half of nsP2. Unexpectedly, the anti-nsP2 MAb 1E9 cross-reacted strongly with a host protein of 78 kDa from uninfected human, murine, avian and insect cells. This protein was identified as the immunoglobulin binding protein, BiP, by 2-D gel mapping and reaction with anti-BiP antiserum.
Albumin induces interleukin-6 release from primary human proximal tubule epithelial cells (2008)

These data demonstrate that albumin induces IL-6 release by primary human PTECs, and support a role for endocytosis, p38 MAPK, ERK1,2 and in this process.
Comparison of Established Cell Lines at Different Passages by Karyotype and Comparative Genomic Hybridization (2004)

Two established cancer cell lines, MCF-7 and Ishikawa, were both obtained directly from a cell repository and through another laboratory. The karyotypes from the two MCF-7 cell lines had up to 83 chromosomes and similarities for chromosomal gain and structural abnormalities. The two Ishikawa cell lines had up to 60 chromosomes with only a missing X as the common chromosome abnormality. CGH studies were performed by co-hybridizing the two Ishikawa or MCF-7 cell lines to normal metaphases. The differences seen between the two MCF-7 cell cultures reflect changes due to passage number and culture conditions. For Ishikawa, DNA polymorphic data and mutation studies suggest that the two cell lines are not derived from the same established tumor cell line. Our study shows the utilization of CGH in comparing cell lines originating from the same specimen. Our study also demonstrates the necessity for periodically evaluating cell lines to confirm their origin.
In vitro interactions between barley TALE homeodomain proteins suggest a role for protein–protein associations in the regulation of Knox gene function (2001)

This paper describes two-hybrid interactions amongst barley homeodomain proteins encoded by the Three Amino acid Loop Extension (TALE) superfamily. The class I KNOX protein BKN3 is shown to homodimerise and to associate with proteins encoded by the class I and II Knox genes BKn-1 and BKn-7. Furthermore, JUBEL1 and JUBEL2, two BELL1 homologous proteins, are identified and characterised as interacting partners of BKN3. Differences in the requirements of BKN3 derivatives for interactions with KNOX and JUBEL proteins imply the involvement of overlapping but slightly different domains. This set of results is an example for interactions amongst different classes of plant TALE homeodomain proteins, as previously described for related animal proteins. Apparently identical spatial and temporal expression patterns of BKn-1, BKn-3, BKn-7, JuBel1 and JuBel2, as determined by in situ hybridisation, are compatible with possible interactions of their protein products in planta. Contradictory to the common model, that the transcriptional down-regulation of certain class 1 Knox-genes is the prerequisite for organ differentiation, transcripts of all five genes were, similar to Tkn1 and Tkn2/LeT6 of tomato, detected in incipient and immature leaves as well as in meristematic tissues. A characteristic phenotype is induced by the overexpression of JuBel2 in transgenic tobacco plants.
Quantitative evaluation of erythropoietic activity in dysmyelopoietic syndromes (1982)

Based on the morphological appearances of the bone marrow and peripheral blood, 43 patients with dysmyelopoietic syndromes were categorized into four types: refractory anaemia with excess of blasts, chronic myelomonocytic leukaemia, primary acquired sideroblastic anaemia and refractory anaemia with cellular marrow, without excess of blasts and/or ring sideroblasts. Ferrokinetics allowed three distinct groups of patients to be defined. All cases of refractory anaemia with excess of blasts and chronic myelomonocytic leukaemia were classified in the same group. They were characterized by relative marrow failure and had a high likelihood of developing acute leukaemia. At the other end of the spectrum, individuals with primary acquired sideroblastic anaemia had high erythropoietic activity which was largely ineffective. They had a benign clinical course without evidence of leukaemic transformation. In the middle group, in terms of erythropoietic activity, lay patients with refractory anaemia with cellular marrow and a few individuals with primary acquired sideroblastic anaemia. Their clinical course and risk of developing acute leukaemia were intermediate between the other two groups. These findings indicate that separate entities may exist within the spectrum of dysmyelopoietic syndromes. In clinical practice, they may be recognized by morphological studies and other simple laboratory means.
Controlling crystal growth with modifiers (2009)

Modifying crystal growth processes using additives is a well established approach to solving problems in many processes. Nature also makes extensive use of crystalline inorganic structures modified by soluble and insoluble organic materials. This Highlight discusses some of the recent and interesting developments in this area, with an emphasis on the control of crystal growth rates, covering both inhibitors and the lesser known promoters of crystal growth. Hybrid materials resulting from the incorporation of modifiers into crystalline structures are also discussed, with an emphasis on non-classical crystallisation mechanisms, involving the oriented attachment of nanoparticles.
Expression and function of the co-stimulator H4/ICOS on activated T cells of patients with rheumatoid arthritis. (2003)

Our results suggest that local immune responses may be modulated by H4/ICOS expressed on T cells in the joints of patients with RA, and thus H4/ICOS may be involved in the pathogenetic mechanism of RA.
Neuroprotective Effects of Alpha-Mangostin on MPP+-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells (2015)

In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP(+)-induced apoptosis. The effects of alpha-mangostin on MPP(+)-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP(+) on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP(+). Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP(+). The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP(+) treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP(+)-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.
Immunogenicity of a 26-Valent Group A Streptococcal Vaccine (2002)

A multivalent vaccine containing amino-terminal M protein fragments from 26 different serotypes of group A streptococci was constructed by recombinant techniques. The vaccine consisted of four different recombinant proteins that were formulated with alum to contain 400 microg of protein per dose. Rabbits were immunized via the intramuscular route at 0, 4, and 16 weeks. Immune sera were assayed for the presence of type-specific antibodies against the individual recombinant M peptides by enzyme-linked immunosorbent assay and for opsonic antibodies by in vitro opsonization tests and indirect bactericidal tests. The 26-valent vaccine was highly immunogenic and elicited fourfold or greater increases in antibody levels against 25 of the 26 serotypes represented in the vaccine. The immune sera were broadly opsonic and were bactericidal against the majority of the 26 different serotypes. Importantly, none of the immune sera cross-reacted with human tissues. Our results indicate that type-specific, protective M protein epitopes can be incorporated into complex, multivalent vaccines designed to elicit broadly protective opsonic antibodies in the absence of tissue-cross-reactive antibodies.