gebhart/patrepeval huggingface dataset:
Phosphoinositide 3-hydroxide kinase blockade enhances apoptosis in the Ewing's sarcoma family of tumors. (1999)

Ewing's sarcoma family of tumors (ESFTs) affects patients between the ages of 3 and 40 years, with most cases occurring in the second decade of life. These tumors contain a characteristic translocation, t(11;22), that produces a unique fusion protein, EWS/FLI-1. EWS/FLI-1 transforms mouse fibroblasts; this transformation requires intact EWS and FLI-1 domains as well as the insulin-like growth factor-I receptor (IGF-IR). The IGF-IR is a well-described transmembrane tyrosine kinase receptor that modulates transformation, cell growth, and survival. IGF-IR survival signaling is mediated through the downstream activation of phosphoinositide 3-OH kinase (PI 3-K) and Akt. Apoptosis, programmed cell death, progresses from a central death signal to a caspase cascade, including activation of caspase-3. Because the IGF-IR has been shown to play a role in the transformation and growth of ESFTs, we wanted to determine the role of downstream molecules in the cellular response to doxorubicin treatment. Doxorubicin increased caspase-3 activity in two ESFT cell lines, TC-32 and TC-71. Concomitant treatment of the doxorubicin-treated cells with IGF-I reduced caspase-3 activity 8-fold in TC-32 and 4-fold in TC-71. To determine whether PI 3-K has a role in IGF-I-mediated survival in ESFTs, PI 3-K was then inhibited with wortmannin and LY294002. Doxorubicin treatment reduced cell number and enhanced apoptosis in PI 3-K inhibited cells compared with noninhibited cells. Akt, a serine/threonine kinase activated downstream of PI 3-K, was investigated to determine whether its constitutive activation would render ESFT cells more resistant to doxorubicin. A constitutively activated Akt was stably transfected into ESFT and those cells with high levels of expression demonstrated increased resistance to doxorubicin-induced caspase-3 activation. These results indicate that ESFT cell lines use an IGF-IR initiated signaling pathway through PI 3-K and Akt for survival when treated with doxorubicin.
Methyl Analogues of the Experimental Alzheimer Drug Phenserine:  Synthesis and Structure/Activity Relationships for Acetyl- and Butyrylcholinesterase Inhibitory Action (2001)

With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition.
A C 35 Carotenoid Biosynthetic Pathway (2003)

Upon coexpression with Erwinia geranylgeranyldiphosphate (GGDP) synthase in Escherichia coli, C(30) carotenoid synthase CrtM from Staphylococcus aureus produces novel carotenoids with the asymmetrical C(35) backbone. The products of condensation of farnesyldiphosphate and GDP, C(35) structures comprise 40 to 60% of total carotenoid accumulated. Carotene desaturases and carotene cyclases from C(40) or C(30) pathways accepted and converted the C(35) substrate, thus creating a C(35) carotenoid biosynthetic pathway in E. coli. Directed evolution to modulate desaturase step number, together with combinatorial expression of the desaturase variants with lycopene cyclases, allowed us to produce at least 10 compounds not previously described. This result highlights the plastic and expansible nature of carotenoid pathways and illustrates how combinatorial biosynthesis coupled with directed evolution can rapidly access diverse chemical structures.
Simulation Based Evaluation of Dynamic Queue Warning System Performance (2013)

Microscopic traffic simulation was used to evaluate various design alternatives of a dynamic queue warning system at a freeway work zone with lane closure. The objectives were to (1) assess the expected performance and reliability of a dynamic queue warning system deployed at a freeway work zone lane closure; (2) evaluate the sensitivity of the system’s performance on key design parameters; and (3) determine the most appropriate settings for these parameters. Various combinations of the following design parameters were studied using microscopic traffic simulations: Speed thresholds - for queue detection and warning message selection; Aggregation interval - for averaging vehicle speeds at each sensor location; Update interval – for updating messages based on portable changeable message sign (PCMS); Detector spacing – distance between speed sensors deployed upstream of the lane closure; PCMS location – defined by their distance to the lane closure. As expected, the queue warning systems with half-mile detector spacing can more accurately detect the end-of-queues than those with 1-mile detector spacing. It was also found that the queue detection and queue length estimation accuracy of the system was not sensitive to the speed thresholds in the 25-35 mph speed range. Therefore, based on safety considerations, 35 mph is recommended as queue detection threshold. The recommended threshold for “slow traffic” messages in freeway applications is 55 mph. The recommended speed aggregation interval is 5 minutes.
Brain image registration based on curve mapping (2002)

A new two-stage approach for brain image registration is proposed. In the first stage, an active contour algorithm is used to establish a length-preserving, one-to-one mapping between the cortical and the ventricular boundaries in the two images to be registered. This mapping is used in the second step by a two-dimensional transformation which is based on an elastic body deformation. This method was tested by registering magnetic resonance images to both photographic pathology images and atlas images.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
MNOS/floating-gate charge coupled devices for high density EEPROMS : A new concept (1998)

CCDs are now mostly used for imaging applications. Other applications as shift registers, recirculating memories, transversal filters, etc. have been almost fully taken over by CMOS. CCDs having metal-nitride-oxide (MNOS) structures or floating polysilicon gates have the potential of being used as high density EEPROMs. In such CCD EEPROMs to be proposed in this paper, each data bit is stored under a single gate electrode occupying much smaller area than a MOSFET used for storing data in conventional MOS EEPROMs. The threshold voltage for each gate can be adjusted by charge pumping to or from the oxide-nitride interface/ polysilicon floating gate. This method can be utilised for storing or erasing/restoring data under the gates bit-by-bit. The stored data can be read out by the standard CCD clocking technique. The paper presents the basic idea and explores certain aspects on the functioning of the memory. It also discusses the technological feasibility and future potential.
The DrosophilaSTIM1 orthologue, dSTIM, has roles in cell fate specification and tissue patterning (2008)

Our studies show that dSTIM regulates growth and patterning of imaginal discs and indicate potential interactions with the Notch and Wingless signaling pathways. These interactions may be relevant to studies implicating STIM family proteins in tumorigenesis.
Tubulin requires tau for growth onto microtubule initiating sites. (1976)

Tubulin purified by phosphocellulose chromatography and free of accessory proteins will not form microtubules in the absence or presence of microtubule initiating sites (flagellar microtubules). The capacity for growth onto pre-existing "seeds" can be restored by the addition of small quantities of partially purified tau protein. Larger quantities restore the capacity for spontaneous assembly. These results suggest that tubulin requires tau for both initiation and growth of microtubules and that tau is incorporated into the microtubule throughout its length.
Lipid-mediated protein delivery of suicide nucleoside kinases. (2003)

Nucleoside kinases from several species are investigated as suicide genes for treatment of malignant tumors by combined gene/chemotherapy. In the present study, we have investigated a novel strategy where nucleoside kinase proteins are directly delivered to cells without delivery of genetic material. We used a mix of a trifluoroacetylated lipopolyamine and dioleoyl phosphatidylethanolamine (BioPorter) to form protein-lipid complexes containing either recombinant herpes simplex virus type-1 thymidine kinase or Drosophila melanogaster multisubstrate deoxyribonucleoside kinase. We showed that the nucleoside kinase containing protein-lipid complexes was imported into human osteosarcoma and Chinese hamster ovary cell lines by endocytosis and that the enzymes were delivered to the cytosol and nucleus. The nucleoside kinases imported into the cell lines retained enzymatic activity, and the cells treated with the enzyme-lipid complexes showed increased sensitivity to nucleoside analogues, such as ganciclovir, (E)-5-(2-bromovinyl)-2'-deoxyuridine, and 1-beta-D-arabinofuranosylthymine. Our results show that direct delivery of suicide gene proteins to cells may be an alternative approach to conventional suicide gene therapy strategies.
Charge Transport and Recombination in Perovskite (CH3NH3)PbI3 Sensitized TiO2 Solar Cells (2013)

We report on the effect of TiO2 film thickness on the charge transport, recombination, and device characteristics of perovskite (CH3NH3)PbI3 sensitized solar cells using iodide-based electrolytes. (CH3NH3)PbI3 is relatively stable in a nonpolar solvent (e.g., ethyl acetate) with a low iodide concentration (e.g., 80 mM). Frequency-resolved modulated photocurrent/photovoltage spectroscopies show that increasing TiO2 film thickness from 1.8 to 8.3 μm has little effect on transport but increases recombination by more than 10-fold, reducing the electron diffusion length from 16.9 to 5.5 μm, which can be explained by the higher degree of iodide depletion within the TiO2 pores for thicker films. The changes of the charge-collection and light-absorption properties of (CH3NH3)PbI3 sensitized cells with varying TiO2 film thickness strongly affect the photocurrent density, photovoltage, fill factor, and solar conversion efficiency. Developing alternative, compatible redox electrolytes is important for (CH3NH3)PbI3 or similar perovskites to be used for potential photoelectrochemical applications.
The Human Immunoglobulin Heavy Variable Genes (1999)

'Human Immunoglobulin Heavy Variable Genes', the fourth report of the 'IMGT Locus on Focus' section, comprises five tables entitled: (1) 'Number of human germline IGHV genes at 14q32.33 and potential repertoire'; (2) 'Human germline IGHV genes at 14q32.33'; (3) 'Human IGHV orphons on chromosome 15 (15q11.2)'; (4) 'Human IGHV orphons on chromosome 16 (16p11.2)', and (5) 'Human IGHV allele table'. These tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cnusc.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.
Binding of epidermal growth factor‐dextran conjugates to cultured glioma cells (1991)

Some gliomas, melanomas and squamous carcinomas have large numbers of EGF receptors which could, in these cases, be used for targeting with toxic agents. We investigated whether EGF could be conjugated to dextran, which is a suitable carrier for toxic agents, without losing its ability to bind to the receptor. Dextran of 20 kDa molecular weight was activated with I-cyano-4-dimethylamino pyridinium tetrafluoroborate (CDAP) yielding highly active pyridinium-isourea derivatives. EGF was coupled to the activated dextran through the amino terminus and glycine was added to block residual activity. The EGF-dextran conjugate was, after purification on Sephadex G25 and Sephacryl 200 columns, tested for its receptor binding properties on human malignant glioma, U343MGaC12:6, cells. The conjugate inhibited binding of 125I-EGF in a competitive assay, showing that the binding was receptor-specific. Dextran conjugated with glycine, without EGF, had no inhibitory effect. The conjugate was radio-labelled either on the EGF part with 125I or on the dextran part with 3H-glycine, and the internalization patterns were compared to the internalization of 125I-EGF. The radioactivity of the conjugates remained cell-associated for more than 20 hr, regardless of whether the radioactivity was on the EGF or on the dextran part, while the radioactivity of unconjugated EGF rapidly disappeared from the cells. Most of the cell-associated radioactivity was, at all analysed time intervals, located intracellularly. Thus, it seems promising to use dextran, conjugated with EGF, as a carrier of, for example, toxic radioactive nuclides.
The Role of Leaf Shape in the Inheritance of Heading in Lettuce (Lactuca sativa L.)1 (1975)

Abstract Leaf index (width/length) was measured in the parental lines, F 1 and F 2 of the cross ‘Gallega’ (rosette type) × ‘Minetto’ (crisphead). The minimum genetic requirement for head formation in the F 2 was probably a combination of 3 genes, 1 dominant and 2 recessive. However, none of the heading segregates fully recovered the ‘Minetto’ phenotype. The heading genotype of ‘Minetto’ differed from that of ‘Gallega’ by a mimimum of 3, and probably 4 or more, predominantly recessive genes. The primary effect of “heading genes” was to increase the leaf index, i.e. produce leaves which were wide at the base.
γ-Heregulin has no biological significance in primary breast cancer (2002)

British Journal of Cancer (2002) 86, 1362–1363. DOI: 10.1038/sj/bjc/6600245 www.bjcancer.com
Protection against experimental cerebral metastases of murine melanoma B16 by active immunization. (1993)

Melanoma patients often develop brain metastases despite effective systemic immunotherapy against melanoma. We have attempted to establish a mouse model to develop strategies to combat this problem. Immunization of C57BL/6 (H-2b) mice with a combination of the syngeneic G3.12/BM2 melanoma (a B16 subclone) and the allogeneic Cloudman-S91 melanoma was effective in preventing the growth of 10,000 viable, s.c. injected G3.12 cells in 93% of the mice. Irradiated whole tumor cells pretreated with gamma-interferon for 2 days were most effective. A nonspecific adjuvant (DETOX) was injected routinely together with the tumor cells. Active immunization with 2 different doses of irradiated melanoma cells (1 x 10(5) or 2.5 x 10(6) cells/injection x 5 injections) protected against intracerebral challenge with 200 live G3.12 cells in 69% of the mice. This challenge caused the death of all control mice within 30 days. T-cell-mediated, tumor-specific cytotoxicity against G3.12 melanoma was demonstrated in the spleen of immunized mice. Histological observations in the brain, 80 days after tumor challenge, indicated complete eradication of the melanoma, but although CD4+ and CD8+ T-cells and macrophages were present, their number was low. Gliosis was present in both immunized and control animals. Thus, in this murine melanoma model syngeneic mice were protected from death by s.c. and intracerebrally inoculated tumor cells if pretreated with a sufficient number of irradiated syngeneic and allogeneic melanoma cells and an immunological adjuvant. Whether this regimen can treat established tumors of the brain, alone or in combination, is uncertain. Yet its success suggests that the "blood-brain barrier" impeding immunity to tumors may not be absolute.
TCR‐independent cytokine stimulation induces non‐MHC‐restricted T cell activity and is negatively regulated by HLA class I (2006)

Recent evidence suggests that the functional status of T cells activated independently from their TCR differs substantially from classical MHC-restricted T cells. Here, we show that TCR-independent, short-term stimulation via the common gamma-chain of the IL-2/IL-15 receptor induces non-MHC-restricted cytotoxicity and sustained cytokine secretion in purified CD4+ or CD8+ T cells. NK-like cytotoxicity is directed against MHC class I-negative targets and can be inhibited by classical and non-classical HLA class I molecules. Known inhibitory receptors, such as CD85j (ILT2) and leukocyte-associated Ig-like receptor-1, are not responsible for this HLA-mediated inhibition. NK-like cytotoxicity can be costimulated by NKG2D (CD314) triggering, but 2B4 (CD244) and DNAM-1 (CD226) are not involved. NK-like T cells display an activated phenotype and secrete various cytokines, including IFN-gamma, TNF-alpha, IL-5, IL-13 and MIP-1beta. Under normal conditions, HLA class I-mediated inhibition may function as a safety mechanism to prevent unbalanced cytokine production and effector killing mechanisms by T cells that were activated independently from their TCR. Non-MHC-restricted activity represents a functional status rather than a property of distinct T cell subpopulations. Thus, cytokine-induced, non-MHC-restricted T cells may be relevant in immune responses against tumors showing aberrant MHC expression through their capacities of cytokine production and direct tumor cell eradication.
Rate control strategy for embedded wavelet videocoders (1999)

An investigation into the use of rate-control strategies for embedded wavelet video encoders is presented. It is shown that the best model for the R-D of these encoders is piecewise linear. Also, an effective iterative procedure is proposed for dealing with the problem of frame dependency, which yields improved rate × distortion results.
Glucocorticoids: Structure, Signaling and Molecular Mechanisms in the Treatment of Diabetic Retinopathy and Diabetic Macular Edema (2014)

Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood pressure and dyslipidemia. Ocular treatments include vascular endothelial growth factor A (VEGF-A) inhibitors, laser photocoagulation and surgery. While anti-VEGF therapy has become as first-line treatment for diabetic macular edema (DME) that causes reduced vision, intravitreal glucocorticoids also have been shown to be efficacious in this situation. It has been reported that all the major pathological processes of DR are susceptible to glucocorticoid treatment. The effects of glucocorticoids on vascular leakage and angiogenesis may be mediated through their well established anti-inflammatory role. Alternatively, glucocorticoids may affect other mechanisms known to be activated in DR. Potential mechanisms for the anti-inflammatory effects of glucocorticoids include blockage of cytokine production and inhibition of leukocyte adhesion induced by VEGF-A. Glucocorticoids decrease the expression of VEGF-A directly, and increase the production, or decrease phosphorylation, of tight junction-associated proteins. Glucocorticoids have also been shown to be neuroprotective, in contrast to VEGF-A inhibitors which animal studies suggest may be neurotoxic. This review outlines the biological properties of synthetic glucocorticoids, with particular emphasis on the potential beneficial effect of combining glucocorticoids with anti-VEGF treatment for DME and DR.
Osteomimetic properties of prostate cancer cells: A hypothesis supporting the predilection of prostate cancer metastasis and growth in the bone environment (1999)

Elucidation of common proteins, presumably driven by the same promoters, expressed by both prostate cancer and bone stromal cells, could result in the development of novel preventive and therapeutic strategies for the treatment of prostate cancer skeletal metastasis. Agents developed using these strategies could have the potential advantage of interfering with growth and enhancing apoptosis in both prostate cancer and bone stromal compartments. The selective application of gene therapy strategy, driven by tissue-specific and tumor-restricted promoters for the safe delivery and expression of therapeutic genes in experimental models of prostate cancer metastasis, is discussed.
Reactivity of Functional Groups on the Protein Surface:  Development of Epoxide Probes for Protein Labeling (2003)

We present the development of new affinity probes for protein labeling based on an epoxide reactive group. Systematic screening revealed that an epoxide functionality possesses the special combination of stability and reactivity which renders it stable toward proteins in solution but reactive on the protein surface outside the active site (proximity-induced reactivity). Highly efficient and selective labeling of purified HCA II (human carbonic anhydrase II) was achieved. For instance, 2 equiv of epoxide probe 9 was sufficient for nearly quantitative labeling of HCA II (>90% yield, 20 h reaction time). MS analysis of the labeled protein revealed that 1 equiv of the probe was attached and that labeling occurred at a single residue (His 64) outside the active site. Importantly, epoxide probe 9 selectively labeled HCA II both in simple protein mixtures and in cellular extracts. In addition to the chemical insight and its relevance to many epoxide-containing natural products, this study generated a promising lead in the development of new affinity probes for protein labeling.
Transition Metals for Selective Chemical Vapor Deposition of Parylene-Based Polymers (2000)

A novel method for realizing selective growth of parylene-N and parylene-C synthesized by chemical vapor deposition is presented. Exposure of surfaces to transition metals, metal salts, and organometallic complexes, such as those of iron, ruthenium, platinum, palladium, copper, and silver, is found to inhibit polymer deposition on the substrate. The maximum thickness of the selectively grown polymer films is dependent on the monomer delivery rate to the surface and metal inhibitor used, and for lower growth rates on surfaces patterned with iron, structures 1.4 μm and 4.1 μm in thickness are realized for parylene-N and parylene-C, respectively. The selectively deposited polymer films show no overgrowth onto the metallized areas of the substrate and the slope of the feature sidewalls is steeper than 1.1.μm/μm. Once polymer nucleation finally occurs on the metal films, the morphology of the deposited polymer layer reflects the effectiveness of the metal in preventing polymer deposition. For substrates with little effect on polymer deposition the film morphology consists of uniformly distributed small nodules reflecting multiple polymer nucleation sites on the surface. When the metal initially inhibits polymer growth, the morphology has significantly larger grains, indicating fewer nucleation sites. Possible mechanisms underlying the selective growth are discussed.
Highly selective 1.55 µm InP/air gap micromachinedFabry-Perot filter for optical communications (1998)

The authors report a highly selective and tunable optical filter at 1.55 µm using a Fabry-Perot resonator with micromachined InP-air gap distributed Bragg reflectors. The resonance full width half maximum, as measured by micro-reflectivity experiments, is close to 0.4 nm (around 1.55 µm) and is compatible with wavelength division multiplexing specifications for optical telecommunications.