gebhart/patrepeval huggingface dataset:
Detection of N-Glycolyl GM3 Ganglioside in Neuroectodermal Tumors by Immunohistochemistry: An Attractive Vaccine Target for Aggressive Pediatric Cancer (2011)

The N-glycolylated ganglioside NeuGc-GM3 has been described in solid tumors such as breast carcinoma, nonsmall cell lung cancer, and melanoma, but is usually not detected in normal human cells. Our aim was to evaluate the presence of NeuGc-GM3 in pediatric neuroectodermal tumors by immunohistochemistry. Twenty-seven archival cases of neuroblastoma and Ewing sarcoma family of tumors (ESFT) were analyzed. Formalin-fixed, paraffin-embedded tumor samples were cut into 5 μm sections. The monoclonal antibody 14F7, a mouse IgG1 that specifically recognizes NeuGc-GM3, and a peroxidase-labeled polymer conjugated to secondary antibodies were used. Presence of NeuGc-GM3 was evident in 23 of 27 cases (85%), with an average of about 70% of positive tumors cells. Immunoreactivity was moderate to intense in most tumors, showing a diffuse cytoplasmic and membranous staining, although cases of ESFT demonstrated a fine granular cytoplasmic pattern. No significant differences were observed between neuroblastoma with and without NMYC oncogene amplification, suggesting that expression of NeuGc-GM3 is preserved in more aggressive cancers. Until now, the expression of N-glycolylated gangliosides in pediatric neuroectodermal tumors has not been investigated. The present study evidenced the expression of NeuGc-GM3 in a high proportion of neuroectodermal tumors, suggesting its potential utility as a specific target of immunotherapy.
c-Jun NH2-terminal Kinases Target the Ubiquitination of Their Associated Transcription Factors (1997)

Regulatory proteins are often ubiquitinated, depending on their phosphorylation status as well as on their association with ancillary proteins that serve as adapters of the ubiquitination machinery. We previously demonstrated that c-Jun is targeted for ubiquitination by its association with inactive c-Jun NH2-terminal kinase (JNK). Phosphorylation by activated JNK protects c-Jun from ubiquitination, thus by prolonging its half-life. In the study reported here, we determined the ability of JNK to target ubiquitination of its other substrates (Elk1 and activating transcription factor 2 (ATF2)) and associated proteins (ATF2 and JunB). We demonstrate that phosphorylation by JNK protects ATF2, but not Elk1, from JNK-targeted ubiquitination. We also show that association of inactive JNK with JunB or ATF2 is necessary to target them for ubiquitination. Unlike its targeting of c-Jun, JNK requires additional cellular components, yet to be identified, to target the ubiquitination of ATF2. Elk1 is phosphorylated by JNK, but JNK neither associates with nor targets Elk1 for ubiquitination. The implications for the dual role of JNK in the regulation of ubiquitination and stability of c-Jun, ATF2, and JunB in normally growing versus stressed cells are discussed.
Asexual Sporulation inAspergillus nidulans (1998)

The formation of mitotically derived spores, called conidia, is a common reproductive mode in filamentous fungi, particularly among the large fungal class Ascomycetes. Asexual sporulation strategies are nearly as varied as fungal species; however, the formation of conidiophores, specialized multicellular reproductive structures, by the filamentous fungus Aspergillus nidulans has emerged as the leading model for understanding the mechanisms that control fungal sporulation. Initiation of A. nidulans conidiophore formation can occur either as a programmed event in the life cycle in response to intrinsic signals or to environmental stresses such as nutrient deprivation. In either case, a development-specific set of transcription factors is activated and these control the expression of each other as well as genes required for conidiophore morphogenesis. Recent progress has identified many of the earliest-acting genes needed for initiating conidiophore development and shown that there are at least two antagonistic signaling pathways that control this process. One pathway is modulated by a heterotrimeric G protein that when activated stimulates growth and represses both asexual and sexual sporulation as well as production of the toxic secondary metabolite, sterigmatocystin. The second pathway apparently requires an extracellular signal to induce sporulation-specific events and to direct the inactivation of the first pathway, removing developmental repression. A working model is presented in which the regulatory interactions between these two pathways during the fungal life cycle determine whether cells grow or develop.
Narrowband Interference Mitigation in DS-UWB Systems (2010)

Interference suppression is important for ultra-wideband (UWB) systems to operate over spectrum occupied by pre-existing narrowband systems. In this letter, we first extend the code-aided interference suppression technique to a direct sequence (DS) UWB system which has been proposed for narrowband interference (NBI) suppression in direct sequence spread spectrum (DSSS) systems. Then, we introduce a new type of spreading sequence, which significantly improves the NBI suppression capability of the code-aided technique. We also discuss a preamble-aided synchronization scheme for utilizing the new type of spreading sequence.
Privacy Concerns in Upcoming Residential and Commercial Demand-Response Systems (2008)

Abstract—We explore the privacy concerns arising from the collection of power consumption data in current and future demand-response systems. We claim that in a lax regulatory environment, the detailed household consumption data gathered by advanced metering projects can and will be repurposed by interested parties to reveal personally identifying information such as an individual’s activities, preferences, and even beliefs. To develop this claim, we begin with an overview of demandresponse technologies and their deployment trends, mentioning both the parties interested in the data and their motivations. We proceed to formalize the notion of privacy and list the types of personal information which can be estimated with current and upcoming monitoring technologies. To support our list, we conduct a small-scale monitoring experiment on a private residence. Our results show that personal information can be estimated with a high degree of accuracy, even with relatively unsophisticated hardware and algorithms. We discuss the implications of our results for future demand-response projects. Our paper concludes with guidelines for data-handling policies which ensure the protection of privacy. Index Terms—NG-SCADA, Protection, Privacy. I.
Crossing the barrier: oxysterols as cholesterol transporters and metabolic modulators in the brain (2006)

A normal brain function requires constant levels of cholesterol, and the need for constancy seems to be higher here than in any other organ. Nature has met this need by isolation of brain cholesterol by a highly efficient blood-brain barrier. As a low synthesis of cholesterol is present in the brain, a mechanism for compensatory elimination is required. A decade ago we made the unexpected finding that the favoured mechanism for this involves conversion into 24S-hydroxycholesterol, followed by diffusion over the blood-brain barrier. Recent studies by us and others on this new pathway have given new insights into the mechanisms by which cholesterol homeostasis is maintained in the brain. We recently demonstrated a flux of another oxygenated product of cholesterol, 27-hydroxycholesterol, in the opposite direction. The latter flux may be important for neurodegeneration, and may be the link between hypercholesterolaemia and Alzheimer's disease. An overview of the above studies is presented and the possibility that the cholesterol 24S-hydroxylase in the brain may be important for memory and learning and that it may be a new drug target is discussed.
Obstacles to acceptance of clinical decision analysis. (1989)

posts are required for clinical academic staff who wish to devote most of their time to research. (17) Similarly, 100 career posts are needed for basic. scientists working in clinical research groups. (18) Funds are required for establishing approximately 50 combined MB and PhD programmes and for restoring adequate public financing of a sufficient number of intercalated BSc degree courses to its previous level. (
Octamer-primed cycle sequencing using dye-terminator chemistry (1998)

Octamer Sequencing Technology, OST, is a method of DNA sequencing using single octamer oligonucleotides to prime cycle sequencing reactions. This sequencing strategy is faster than a traditional primer-walking strategy, since access to this optimized octamer library eliminates delays associated with designing and synthesizing gene specific primers. In this report, OST has been optimized for fluorescent, dye-terminator cycle sequencing reactions to facilitate parallel processing of samples. The successful adaptation of OST to an automated sequencing platform and the design of and access to an octamer library are critical steps towards developing an efficient 'closed-loop' DNA sequencing system.
Chemically Induced Degradation of Sirtuin 2 (Sirt2) by a Proteolysis Targeting Chimera (PROTAC) Based on Sirtuin Rearranging Ligands (SirReals) (2017)

Here we report the development of a proteolysis targeting chimera (PROTAC) based on the combination of the unique features of the sirtuin rearranging ligands (SirReals) as highly potent and isotype-selective Sirt2 inhibitors with thalidomide, a bona fide cereblon ligand. For the first time, we report the formation of a PROTAC by Cu(I)-catalyzed cycloaddition of a thalidomide-derived azide to an alkynylated inhibitor. This thalidomide-derived azide as well as the highly versatile linking strategy can be readily adapted to alkynylated ligands of other targets. In HeLa cells, our SirReal-based PROTAC induced isotype-selective Sirt2 degradation that results in the hyperacetylation of the microtubule network coupled with enhanced process elongation. Thus, our SirReal-based PROTAC is the first example of a probe that is able to chemically induce the degradation of an epigenetic eraser protein.
Mapping and pseudoinverse algorithms for ocean data assimilation (2003)

Among existing ocean data assimilation methodologies, reduced-state Kalman filters are a widely studied compromise between resolution, optimality, error specification, and computational feasibility. In such reduced-state filters, the measurement update takes place on a coarser grid than that of the general circulation model (GCM); therefore, these filters require mapping operators from the GCM grid to the reduced state and vice versa. The general requirements are that the state-reduction and interpolation operators be pseudoinverses of each other, that the coarse state define a closed dynamical system, that the mapping operations be insensitive to noise, and that they be appropriate for regions with irregular coastlines and bathymetry. In this paper, we describe three efficient algorithms for computing the pseudoinverse: a fast Fourier transform algorithm that serves for illustration purposes, an exact implicit method that is recommended for most applications, and an efficient iterative algorithm that can be used for the largest problems. The mapping performance of 11 interpolation kernels is evaluated. Surprisingly, common kernels such as bilinear, exponential, Gaussian, and sinc perform only moderately well. We recommend instead three kernels, smooth, thin-plate, and optimal interpolation, which have superior properties. This study removes the computational bottleneck of mapping and pseudoinverse algorithms and makes possible the application of reduced-state filters to global problems at state-of-the-art resolutions.
Functional Complementation in Escherichia coli of Different Phytoene Desaturase Genes and Analysis of Accumulated Carotenes (1991)

Three different phytoene desaturase genes, from Rhodobacter capsulatus, Erwinia uredovora, and Synechococcus PCC 7942, have been functionally complemented with a gene construct from E. uredovora which encodes all enzymes responsible for formation of 15-cis phytoene in Escherichia coli. As indicated by the contrasting reaction products detected in the pigmented E. coli cells after co-transformation, a wide functional diversity of these three different types of phytoene desaturases can be concluded. The carotenes formed by the phytoene desaturase from R. capsulatus were trans-neurosporene with three additional double bonds and two cis isomers. Furthermore, small amounts of three zeta-carotene isomers (2 double bonds more than phytoene) and phytofluene (15-cis and all-trans with + 1 double bond) were detected as intermediates. When the subsequent genes from E. uredovora which encode for lycopene cyclase and beta-carotene hydroxylase were present, neurosporene, the phytoene desaturase product of R. capsulatus, was subsequently converted to the monocyclic beta-zeacarotene and its monohydroxylation product. The most abundant carotene resulting from phytoene desaturation by the E. uredovora enzyme was trans-lycopene together with a cis isomer. In addition, bisdehydrolycopene was also formed. The reaction products of Synechococcus phytoene desaturase were two cis isomers of zeta-carotene and only small amounts of trans-zeta-carotene including 15-cis. The I50 values for flurtamone and diphenylamine to inhibit phytoene desaturation were determined and differential inhibition was observed for diphenylamine.
Lung Disease, Indigestion, and Two-way Tables (2015)

AbstractThis paper considers the responses of 115 school students to two problems based on information provided in two-way tables. In each case the question asks if one of the variables involved depends on the other. Contextual knowledge might suggest a dependent relationship in both but in one problem the data show independence while in the other the data imply an inverse relationship. A wide range of solution strategies illustrates the cognitive complexity dealing with information in two-way tables.
Analytic model of the ion angular distribution in a collisional sheath (1993)

An analytic model is developed for the ion angular distribution in a collisional sheath. In a previous study, the one-dimensional (normal to the sheath) ion velocity distribution was obtained under the assumption that charge exchange is the dominant ion-neutral collision mechanism. In the present model, we assume λscat≥λcx, where λscat and λcx are the mean free paths for ion-neutral elastic scattering and charge-exchange collisions, respectively. With this assumption, the angular distribution mainly arises from ions that strike the electrode after undergoing only one scattering collision following the last charge-exchange collision. Comparison of the analytic model with results obtained from a particle-in-cell simulation gives excellent agreement. Both the average angle of ions striking the electrode and the ratio of parallel to perpendicular ion flux at the electrode are shown to scale with the ratio of scattering to charge-exchange cross sections σscat/σcx.
PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases (2016)

One of the major immune checkpoints responsible for immune evasion in cancer cells is the interaction between programmed cell death-1 (PD-1) and its ligand (PD-L1). As human trophoblastic cells display many of the features of malignant cells such as the ability to invade normal tissue including blood vessels and are apparently not eradicated by the host immune system, we undertook the present study to determine whether PD-L1 was upregulated in different types of trophoblastic cells during normal pregnancy and in gestational trophoblastic diseases. Immunohistochemistry using an anti-PD-L1-specific antibody demonstrated that in early and term normal placentas, PD-L1 was highly expressed in syncytiotrophoblast and to a much lower extent in intermediate trophoblastic cells located in the chorion laeve and implantation site. PD-L1 immunoreactivity was undetectable in cytotrophoblastic cells. This staining pattern in normal placenta was recapitulated in various types of gestational trophoblastic disease. PD-L1 was highly expressed by syncytiotrophoblast in complete moles and choriocarcinomas. The intermediate trophoblastic neoplasms, placental site trophoblastic tumors, and epithelioid trophoblastic tumors showed variable PD-L1 immunoreactivity but at a lower intensity than in the neoplastic syncytiotrophoblast in choriocarcinoma. In addition, we observed PD-1-positive lymphocytes located within the implantation site and in trophoblastic tumors. In summary, this study describes a novel mechanism for trophoblastic cells to create a tolerogenic feto-maternal interface by upregulating PD-L1 in syncytiotrophoblast and in intermediate trophoblast. Trophoblastic tumors may also use PD-L1 expression to evade the host immune response thereby promoting their survival.
Acantholytic variant of squamous cell carcinoma of the breast (2010)

ABSTRACT Acantholytic variant of squamous cell carcinoma (AVSCC) of the breast typically has pseudoglandular or pseudoangiosarcomatous histopathologic features due to marked dyscohesiveness of tumor cells which have dense squamoid cytoplasm. Tumor cells show immunoexpression for cytokeratin AE1/AE3, high molecular weight cytokeratin and p63, thus pertaining squamous characteristics. We present a typical case of AVSCC of the breast with preoperative metastasis to a sentinel lymph node and one‐time recurrence. The tumor was predominantly composed of acantholytic component with minor contribution of patternless spindle cell component. Multifocal intraductal carcinomas were found within the tumor. Although some reports had mentioned about other breast cancers focally showing these characteristic features in usual invasive ductal carcinomas or metaplastic carcinomas, only nine cases have been collected as this recently defined entity since 1986. It is suggested that this tumor would be more aggressive than usual invasive ductal carcinomas based on the original report of three cases. However, additional cases of AVSCC often did not show dismal prognostic outcome. We present a typical case of AVSCC of the breast without critical progression of the disease for 38 months.
Structure−Activity Relationship Studies of Nordihydroguaiaretic Acid Inhibitors toward Soybean, 12-Human, and 15-Human Lipoxygenase (2002)

Lipoxygenase (LO) is a biological target for many diseases such as asthma, atherosclerosis, and cancer. Our labs have synthesized and investigated nordihydroguaiaretic acid (NDGA) derivatives and have established that the reductive inhibition of soybean and 15-human LO can be affected by the strength of the electron-withdrawing substituents on the phenyl rings of NDGA. In addition, we have determined that hydrophobic NDGA derivatives activate 15-HLO, suggesting a hydrophobic allosteric site.
A cDNA clone of the hnRNP C proteins and its homology with the single-stranded DNA binding protein UP2 (1986)

A cDNA clone which expresses a protein that cross-reacts immunologically with the human C1 and C2 hnRNP core proteins has been isolated. The clone was selected by a sensitive immunochemical assay employing an avidin-biotin complex for detection, and identified as a clone for the hnRNP C proteins by a highly sensitive antibody select assay that is described here. The clone contains 677 nucleotides, and, as shown by northern blotting, is derived from a 1.5 Kb poly(A)+ mRNA. There are regions of strong homology between the human and mouse genes, weak homology is seen with chicken DNA, and very little, if any, homology can be detected with Drosophila, Artemia, sea urchin, or yeast DNAs. Two peptides (a total of 24 amino acids) of the calf thymus single-stranded DNA binding protein UP2 show perfect homology with the deduced amino acid sequence of the clone, suggesting that UP2 is related to the hnRNP C proteins. There is also a region that has a sequence very similar to two regions of the single-stranded DNA binding protein UP1 that contain proposed DNA binding sites.
Cooperative Interaction between α- and β-Chains of Hepatocyte Growth Factor on c-Met Receptor Confers Ligand-induced Receptor Tyrosine Phosphorylation and Multiple Biological Responses (1998)

Hepatocyte growth factor (HGF) is a heterodimeric molecule composed of the alpha-chain containing the N-terminal hairpin domain, four kringle domains, and the serine protease-like beta-chain. We prepared HGF/NK4 and HGF/beta from the entire HGF after single-cut digestion with elastase. HGF/NK4 contains the N-terminal hairpin and four kringle domains, while HGF/beta is composed of the C-terminal 16 amino acids of the alpha-chain and the entire beta-chain, linked by a disulfide bridge. HGF/NK4 competitively inhibited the binding of 125I-HGF to the receptor, and affinity cross-linking analysis indicated that HGF/NK4 alone can bind to the c-Met receptor. In contrast, HGF/beta alone did not competitively inhibit the binding of 125I-HGF to the receptor and did not bind to the c-Met/HGF receptor. Scatchard analysis and affinity cross-linking experiments indicated that HGF/beta specifically binds to c-Met in the presence of HGF/NK4 but not HGF/NK2. Neither HGF/NK4 nor HGF/beta alone induced mitogenic, motogenic (cell scattering), and morphogenic (induction of branching tubulogenesis) responses; however, HGF/beta did induce these biological responses in the presence of HGF/NK4. Consistent with these results, although neither HGF/NK4 alone nor HGF/beta alone induced tyrosine phosphorylation of the c-Met/HGF receptor, HGF/beta induced tyrosine phosphorylation of the receptor when c-Met/HGF receptor was occupied by HGF/NK4. These results indicate that HGF/beta binds to the c-Met/HGF receptor that is occupied by HGF/NK4 and induces receptor tyrosine phosphorylation and the subsequent biological activities of HGF. We propose that there exists a unique cooperative interaction between alpha- and beta-chains, this interaction leading to beta-chain-dependent receptor tyrosine phosphorylation and subsequent biological responses.
Dye‐enhanced laser tissue welding (1989)

For vascular anastomosis, use of topical photosensitizing dye enhances selective delivery of laser energy to target tissue, thus reducing the amount of collateral thermal injury and threshold power required for welding. For fluorescein isothiocyanate (FITC)--stained rabbit aorta in vitro, the threshold for tissue blanching was 15 seconds of 100 mW exposure of cw argon ion laser compared with 15 seconds at 300 mW for unstained tissue. The threshold power density needed for argon laser welding of abdominal aortotomies in rabbits in vivo was 3.8 W/cm2 with FITC and 7.6 W/cm2 without the dye. However, bursting pressures for the two groups (164 mm Hg with FITC, 147 mm Hg without FITC) were not significantly different. Histology revealed decreased collateral thermal damage in FITC-enhanced welds. Use of photosensitizing dyes for tissue welding is feasible and may allow arterial welding with lower power laser systems and cause less thermal trauma by lowering threshold power levels.