gebhart/patrepeval huggingface dataset:
Tyrphostins Inhibit Epidermal Growth Factor (EGF)-Receptor Tyrosine Kinase Activity in Living Cells and EGF-Stimulated Cell Proliferation (1989)

Synthetic compounds called tyrphostins were examined for their effects on cells which are mitogenically responsive to epidermal growth factor (EGF). We studied in detail the effects of two tyrphostins on EGF binding, tyrosine phosphorylation in intact cells, EGF-receptor internalization, and mitogenesis. These compounds inhibited EGF-stimulated [3H]thymidine incorporation in a specific manner and the degree of selectivity varied. Both compounds inhibited EGF-stimulated receptor autophosphorylation and tyrosine phosphorylation of endogenous substrates in intact cells at doses that correlated with the IC50 for [3H] thymidine incorporation. These results are consistent with the notion that tyrosine phosphorylation is a crucial signal in transduction of the mitogenic message delivered by EGF. The compound RG50864 demonstrated specificity at inhibiting EGF-stimulated cell growth compared with stimulation with either platelet-derived growth factor or serum. For both compounds RG50864 and RG50810, long term exposure (16 h) of cells to tyrphostins was required for optimal inhibition because of the instability and slow action of these compounds. Tyrphostins did not alter cell surface display of EGF-receptor, EGF binding or EGF-induced internalization, degradation, and down-regulation of EGF receptors. These novel synthetic inhibitors, specific for EGF-receptor kinase, offer a new method to inhibit EGF-stimulated cell proliferation which may be useful in treating specific pathological conditions involving cellular proliferation, including different types of cancers.
The design of a hyperstable mutant of the Abp1p SH3 domain by sequence alignment analysis (2000)

We have characterized the thermodynamic stability of the SH3 domain from the Saccharomyces cerevisiae Abp1p protein and found it to be relatively low compared to most other SH3 domains, with a Tm of 60 degrees C and a deltaGu of 3.08 kcal/mol. Analysis of a large alignment of SH3 domains led to the identification of atypical residues at eight positions in the wild-type Abp1p SH3 domain sequence that were subsequently replaced by the residue seen most frequently at that position in the alignment. Three of the eight mutants constructed in this way displayed increases in Tm ranging from 8 to 15 degrees C with concomitant increases in deltaGu of up to 1.4 kcal/mol. The effects of these substitutions on folding thermodynamics and kinetics were entirely additive, and a mutant containing all three was dramatically stabilized with a Tm greater than 90 degrees C and a deltaGu more than double that of the wild-type domain. The folding rate of this hyperstable mutant was 10-fold faster than wild-type, while its unfolding rate was fivefold slower. All of the stabilized mutants were still able to bind a target peptide with wild-type affinity. We have analyzed the stabilizing amino acid substitutions isolated in this study and several other similar sequence alignment based studies. In approximately 25% of cases, increased stability can be explained by enhanced propensity of the substituted residue for the local backbone conformation at the mutagenized site.
논문 : 합병기업 규모효과의 산술적 요인에 대한 연구 (2010)

합병공시에 따른 합병기업의 주가수익률 행태에서 합병기업 규모효과라는 현상이 존재하고 있음이 지속적으로 보고되고 있다. 본 연구는 합병기업의 규모효과를 `절대수익형 규모효과`와 `상대수익형 규모효과`로 구분한다. 절대수익형 규모효과는 합병공시로 인하여 소규모기업은 양(+)의 비정상수익률을 보이지만 대규모 합병기업은 음(-)의 비정상수익률을 보이는 경향이 있다는 것이고, 상대수익형 규모효과는 합병공시로 인하여 소규모 합병기업과 대규모 합병기업은 모두 양(+)의 비정상수익률을 보이지만 소규모기업이 대규모기업보다 상대적으로 높은 비정상수익률을 보이는 것을 의미한다. 본 연구는 상대수익형 규모효과의 대부분이 경제적 요인이 아닌산술적 요인에 의해서 유도될 수 있음을 논리적으로 밝히고, 이를 실증적으로 검증한 후, 산술적 요인이 제거된 합병성과에 영향을 주는 요인을 분석하였다. 본 연구의 기여도로서는 합병성과를 CAR로 측정할 경우 비경제적인 산술적 규모효과가 개입되기 때문에 이러한 효과를 제거할 필요성을 제기하였고, 산술적 규모효과를 제거하는 절차를 제안하였다는 점을 들 수 있다.
Small-Molecule-Driven Hepatocyte Differentiation of Human Pluripotent Stem Cells (2015)

The differentiation of pluripotent stem cells to hepatocytes is well established, yet current methods suffer from several drawbacks. These include a lack of definition and reproducibility, which in part stems from continued reliance on recombinant growth factors. This has remained a stumbling block for the translation of the technology into industry and the clinic for reasons associated with cost and quality. We have devised a growth-factor-free protocol that relies on small molecules to differentiate human pluripotent stem cells toward a hepatic phenotype. The procedure can efficiently direct both human embryonic stem cells and induced pluripotent stem cells to hepatocyte-like cells. The final population of cells demonstrates marker expression at the transcriptional and protein levels, as well as key hepatic functions such as serum protein production, glycogen storage, and cytochrome P450 activity.
The RTX toxins of Gram-negative bacterial pathogens (1996)

The RTX toxins are a group of calcium-dependent, pore-forming cytolysins secreted by several species of Gram-negative bacteria. They share common structural and functional features, the most prominent of which is a series of glycine-rich nonapeptide repeat units found at the C-terminal end of the proteins from which the designation 'Repeats in ToXin' is derived. These units bind calcium which is important for the subsequent interaction of the toxin with a mammalian target cell. All the toxins are able to form pores in eukaryotic cells membranes which promote osmotic swelling and eventual cell lysis. However, the toxins vary in their degree of cytolytic activity towards different mammalian cells; some will attack red blood cells and leukocytes from a variety of mammalian species whereas others are more species-specific. Their principal role as virulence factors is to modulate the host immune response. At high concentrations they can kill immune effector cells at the primary site of infection which can lead to host tissue damage and a secondary inflammatory response. At sub-lytic concentrations they can promote the release of inflammatory mediators from granulocytes and monocytes, damage endothelial cells and compromise the humoral immune system by inhibition of lymphocyte proliferation and antigen presentation by macrophages.
Isolation of cDNAs encoding a human protein that binds selectively to DNA modified by the anticancer drug cis-diamminedichloroplatinum(II) (1989)

DNA modified by the antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP or cisplatin) was used to identify a factor in mammalian cells that binds to cis-DDP-damaged DNA and hence may play a role in repair. This factor selectively recognizes double-stranded DNA fragments modified by cis-DDP or [Pt(en)Cl2] (en, ethylenediamine). Little or no binding occurs to unmodified double-stranded DNA or to DNA modified with the clinically ineffective compounds trans-DDP and [Pt(dien)Cl]Cl (dien, diethylenetriamine). Low levels of binding to single-stranded DNA modified by cis-DDP are observed. The apparent molecular mass of the factor in a variety of mammalian cells is approximately 100 kDa, as determined by modified Western blotting. Two recombinant phage have been isolated from a human B-cell lambda gt11 library by using a cis-DDP-modified DNA restriction fragment as a probe. The two clones have insert sizes of 1.88 and 1.44 kilobases and are aligned at their 5' ends. The polypeptides encoded by the recombinant phage exhibit DNA binding properties similar to those of the cellular factor identified in crude extracts prepared from mammalian cells. Northern analysis with one of the clones revealed an mRNA of 2.8 kilobases that is conserved in humans and rodents. The methods used here should be applicable in studies of other damage-specific DNA binding proteins.
Transforming growth factor-alpha immunoreactivity during induced hair follicle growth cycles in sheep and ferrets. (1996)

Transforming growth factor-alpha (TGF-alpha) has been associated with cell proliferation of keratinocytes and implicated in hair growth. We therefore examined changes in the immunocytochemical localization of TGF-alpha and cell proliferation markers in the skin of two unrelated species in which hair cycles could be induced, to elucidate the role of this growth factor in the control of fiber growth. Skin was collected from melatonin-treated ferrets (Mustela putorius furo), untreated Romney sheep (Ovis aries), and New Zealand Wiltshire sheep in which interruption of wool growth had been photoperiodically induced. Immunostaining patterns were very similar in ferrets and sheep. TGF-alpha immunoreactivity was observed in epithelial tissues of the skin but was not co-localized with cell proliferation markers. In anagen follicles, specific staining was most intense in the innermost cells of the outer root sheath and cortical cells in the keratogenous zone but was absent from inner root sheath or dermal papilla. TGF-alpha immunostaining diminished during catagen, although faint staining was retained in all epithelial cells. In telogen and early proanagen follicles, staining remained faint or was restricted to cells on the margin of the brush end and follicle neck. Immunoreactivity in the outer root sheath was reestablished in late proanagen. Sebaceous glands and epidermis were stained intensely throughout the hair cycle. TGF-alpha-immunoreactive components of skin extracts, analyzed by Western blotting, showed mobility corresponding to approximately 32 KD, but not to the size of the fully cleaved peptide. These results are consistent with an epithelial autocrine or juxtacrine, but not a mitogenic, function of TGF-alpha.
Mycobacterium Species Identification and Rifampin Resistance Testing with High-Density DNA Probe Arrays (1999)

Species identification within the genus Mycobacterium and subsequent antibiotic susceptibility testing still rely on time-consuming, culture-based methods. Despite the recent development of DNA probes, which greatly reduce assay time, there is a need for a single platform assay capable of answering the multitude of diagnostic questions associated with this genus. We describe the use of a DNA probe array based on two sequence databases: one for the species identification of mycobacteria (82 unique 16S rRNA sequences corresponding to 54 phenotypical species) and the other for detecting Mycobacterium tuberculosis rifampin resistance (rpoB alleles). Species identification or rifampin resistance was determined by hybridizing fluorescently labeled, amplified genetic material generated from bacterial colonies to the array. Seventy mycobacterial isolates from 27 different species and 15 rifampin-resistant M. tuberculosis strains were tested. A total of 26 of 27 species were correctly identified as well as all of the rpoB mutants. This parallel testing format opens new perspectives in terms of patient management for bacterial diseases by allowing a number of genetic tests to be simultaneously run.
Rhizavidin from Rhizobium etli: the first natural dimer in the avidin protein family (2007)

Rhizobium etli CFN42 is a symbiotic nitrogen-fixing bacterium of the common bean Phaseolus vulgaris. The symbiotic plasmid p42d of R. etli comprises a gene encoding a putative (strept)avidin-like protein, named rhizavidin. The amino acid sequence identity of rhizavidin in relation to other known avidin-like proteins is 20-30%. The amino acid residues involved in the (strept)avidin-biotin interaction are well conserved in rhizavidin. The structural and functional properties of rhizavidin were carefully studied, and we found that rhizavidin shares characteristics with bradavidin, streptavidin and avidin. However, we found that it is the first naturally occurring dimeric protein in the avidin protein family, in contrast with tetrameric (strept)avidin and bradavidin. Moreover, it possesses a proline residue after a flexible loop (GGSG) in a position close to Trp-110 in avidin, which is an important biotin-binding residue. [3H]Biotin dissociation and ITC (isothermal titration calorimetry) experiments showed dimeric rhizavidin to be a high-affinity biotin-binding protein. Its thermal stability was lower than that of avidin; although similar to streptavidin, it was insensitive to proteinase K. The immunological cross-reactivity of rhizavidin was tested with human serum samples obtained from cancer patients exposed to (strept)avidin. No significant cross-reactivity was observed. The biodistribution of the protein was studied by SPECT (single-photon emission computed tomography) imaging in rats. Similarly to avidin, rhizavidin was observed to accumulate rapidly, mainly in the liver. Evidently, rhizavidin could be used as a complement to (strept)avidin in (strept)avidin-biotin technology.
A clustering technique for random data classification (2002)

This paper introduces a new clustering technique for random data classification based on an enhanced version of the Voronoi diagram. This technique is optimized to deal in the best way possible with data distributions which experience overlap in their geometric constructs. A thorough analysis is provided in dealing with the dilemmas imposed by the regions of overlap over the prospect of proper data classification. A mathematical framework is given in view of this enhanced analysis and with respect to the description of real-world data through superposition of Gaussian distributions. Computer results prove the soundness of this clustering technique.
Glycogen Synthase Kinase-3 Inactivation Is Not Required for Ischemic Preconditioning or Postconditioning in the Mouse (2008)

The inactivation of glycogen synthase kinase-3beta (GSK-3beta) is proposed as the event integrating protective pathways initiated by preconditioning and other interventions. The inactivation of GSK-3 is thought to decrease the probability of opening of the mitochondrial permeability transition pore. The aim of this study was to verify the role of GSK-3 using a targeted mouse line lacking the critical N-terminal serine within GSK-3beta (Ser9) and the highly homologous GSK-3alpha (Ser21), which when phosphorylated results in kinase inactivation. Postconditioning with 10 cycles of 5 seconds of reperfusion/5 seconds of ischemia and preconditioning with 6 cycles of 4 minutes of ischemia/6 minutes of reperfusion, similarly reduced infarction of the isolated perfused mouse heart in response to 30 minutes of global ischemia and 120 minutes of reperfusion. Preconditioning caused noticeable inactivating phosphorylation of GSK-3. However, both preconditioning and postconditioning still protected hearts of homozygous GSK-3 double knockin mice. Moreover, direct pharmacological inhibition of GSK-3 catalytic activity with structurally diverse inhibitors before or after ischemia failed to recapitulate conditioning protection. Nonetheless, cyclosporin A, a direct mitochondrial permeability transition pore inhibitor, reduced infarction in hearts from both wild-type and homozygous GSK-3 double knockin mice. Furthermore, in adult cardiac myocytes from GSK-3 double knockin mice, insulin exposure was still as effective as cyclosporin A in delaying mitochondrial permeability transition pore opening. Our results, which include a novel genetic approach, suggest that the inhibition of GSK-3 is unlikely to be the key determinant of cardioprotective signaling in either preconditioning or postconditioning in the mouse.
Optical FM Signal Amplification by Injection Locked and Resonant Type Semiconductor Laser Amplifiers (1982)

Optical FM signal amplification by semiconductor lasers is studied by emphasizing their bandwidth characteristics. The laser is operated either in an injection-locked mode or in a resonant amplification mode by keeping the drive current above or just below its threshold. The bandwidths of both amplifiers are evaluated by the reduction in modulation sidebands and are compared with the bandwidths measured statically by scanning the frequency of incident CW wave. The radic G = 25 GHz gain bandwidth product is obtained for both operation modes using a double heterostructure AlGaAs semiconductor laser. The bandwidth obtained in the above procedure is in good agreement with theoretical results.
Challenges for standards for consumer robotics (2006)

For many years, the robotics community has aimed at developing a standard control architecture for robotics. Is this a reasonable goal to pursue? In this paper we discuss this question and other related questions. We describe our philosophy for developing an architecture and describe the key elements of the evolution robotics software platform and architecture.
Differential expression of Protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples (2004)

Protease activated receptors (PAR) form a family of G-protein coupled receptors (GPCR) encoding their own ligands and uniquely activated via proteolytic cleavage. Although proteases in general have been implicated in the remodeling of the extracellular tumor microenvironment, the role of cell surface receptors activated by proteolysis is now emerging. In our present study we investigated the expression pattern of protease activated receptor 1 hPar1 in ovarian carcinoma tissue samples. Abundant hPar1 mRNA and protein were detected in "low malignant potential" and in invasive carcinomas, regardless of the histological subtype. In contrast, no hPar1 expression was detected on the cell surface of normal ovarian epithelium. The differential expression pattern of hPar1 was shown by in situ hybridization, immunohistochemistry and semi-quantitative RT-PCR analyses. In early stages of ovarian carcinoma (Ia), the contra lateral normal ovary showed strong PAR1 expression as opposed to the lack of expression in the ovarian epithelium obtained from normal individuals. In parallel, we analyzed the expression pattern of alphavbeta5 integrin and of activated focal adhesion kinase (FAK), a major focal contact protein, in these tissues. Although abundant expression of alphavbeta5 integrin was observed in all tissues specimens examined, regardless of either normal or malignant, the level of activated FAK was differentially expressed. Phosphorylated FAK was seen in invasive ovarian carcinoma, but not in the normal ovarian epithelium. The abundant hPar1 levels in pathological malignant ovarian carcinoma is likely to transmit signals leading to the phosphorylation of FAK and thereby alterations in the integrin functional state. Altogether our data suggest that hPar1 and FAK cooperate to promote ovarian cancer malignancy.
Perforin forms transient pores on the target cell plasma membrane to facilitate rapid access of granzymes during killer cell attack (2013)

Cytotoxic lymphocytes serve a key role in immune homeostasis by eliminating virus-infected and transformed target cells through the perforin-dependent delivery of proapoptotic granzymes. However, the mechanism of granzyme entry into cells remains unresolved. Using biochemical approaches combined with time-lapse microscopy of human primary cytotoxic lymphocytes engaging their respective targets, we defined the time course of perforin pore formation in the context of the physiological immune synapse. We show that, on recognition of targets, calcium influx into the lymphocyte led to perforin exocytosis and target cell permeabilization in as little as 30 seconds. Within the synaptic cleft, target cell permeabilization by perforin resulted in the rapid diffusion of extracellular milieu-derived granzymes. Repair of these pores was initiated within 20 seconds and was completed within 80 seconds, thus limiting granzyme diffusion. Remarkably, even such a short time frame was sufficient for the delivery of lethal amounts of granzymes into the target cell. Rapid initiation of apoptosis was evident from caspase-dependent target cell rounding within 2 minutes of perforin permeabilization. This study defines the final sequence of events controlling cytotoxic lymphocyte immune defense, in which perforin pores assemble on the target cell plasma membrane, ensuring efficient delivery of lethal granzymes.
Compact broadband polarizer based on shallowly-etched silicon-on-insulator ridge optical waveguides (2010)

A new way to make broadband polarizers on silicon-on-insulator (SOI) waveguides is proposed, analyzed and characterized. The characteristics of the eigenmodes in a shallowly-etched SOI ridge optical waveguide are analyzed by using a full-vectorial finite-different method (FV-FDM) mode solver. The theoretical calculation shows that the loss of TE fundamental mode could be made very low while at the same time the TM fundamental mode has very large leakage loss, which is strongly dependent on the trench width. The leakage loss of the TM fundamental mode changes quasi-periodically as the trench width w(tr) varies. The formula of the period ∆w(tr) is given. By utilizing the huge polarization dependent loss of this kind of waveguide, a compact and simple optical polarizer based on a straight waveguide was demonstrated. The polarizer is fabricated on a 700 nm-thick SOI wafer and then characterized by using a free-space optical system. The measured extinction ratio is as high as 25 dB over a 100 nm wavelength range for a 1 mm-long polarizer.
Optic Vesicle-like Structures Derived from Human Pluripotent Stem Cells Facilitate a Customized Approach to Retinal Disease Treatment (2011)

Differentiation methods for human induced pluripotent stem cells (hiPSCs) typically yield progeny from multiple tissue lineages, limiting their use for drug testing and autologous cell transplantation. In particular, early retina and forebrain derivatives often intermingle in pluripotent stem cell cultures, owing to their shared ancestry and tightly coupled development. Here, we demonstrate that three-dimensional populations of retinal progenitor cells (RPCs) can be isolated from early forebrain populations in both human embryonic stem cell and hiPSC cultures, providing a valuable tool for developmental, functional, and translational studies. Using our established protocol, we identified a transient population of optic vesicle (OV)-like structures that arose during a time period appropriate for normal human retinogenesis. These structures were independently cultured and analyzed to confirm their multipotent RPC status and capacity to produce physiologically responsive retinal cell types, including photoreceptors and retinal pigment epithelium (RPE). We then applied this method to hiPSCs derived from a patient with gyrate atrophy, a retinal degenerative disease affecting the RPE. RPE generated from these hiPSCs exhibited a disease-specific functional defect that could be corrected either by pharmacological means or following targeted gene repair. The production of OV-like populations from human pluripotent stem cells should facilitate the study of human retinal development and disease and advance the use of hiPSCs in personalized medicine.
An Outward-Appearance Patent-Image Retrieval Approach Based on the Contour-Description Matrix (2007)

Since there are mass of images in the outward-appearance patent-image database, a retrieval approach developed for this database is greatly demanded. The shape information of the patent image is the key feature for a patent image. Therefore, we present an outward-appearance patent images retrieval approach based on contour- description matrix. This matrix represents the 2D shape feature and shows the angular and radial distributing information. The proposed representation is invariant to scale, translation and rotation. Our experiments show that the contour-based technique performs significantly better compared to wavelet-based approach previously proposed in the literature. Key words: shape retrieval; patent image