gebhart/patrepeval huggingface dataset:
Interferon/STAT1 and neuregulin signaling pathways are exploratory biomarkers of cetuximab (Erbituxï¿½) efficacy in KRAS wild-type squamous carcinomas: A pathway-based analysis of whole human-genome microarray data from cetuximab-adapted tumor cell-line models (2011)

KRAS mutation status is being used as the sole biomarker to predict therapeutic efficacy of cetuximab in metastatic colorectal cancer (mCRC). A significant number of mCRC patients with KRAS wild-type (WT) tumors, however, do not benefit from cetuximab. We are also lacking efficacy predictors in head and neck squamous cell carcinomas with an intact KRAS signaling and in non-small cell lung cancer in which KRAS mutations do not predict cetuximab efficacy. We recently established pre-clinical models of EGFR gene-amplified KRAS WT A431 squamous carcinoma cells chronically adapted to grow in the presence of cetuximab. We employed the ingenuity pathway analysis software to functionally interpret data from Agilent's whole human genome arrays in the context of biological processes, networks, and pathways. Cetuximab-induced activation of the interferon (IFN)/STAT1 appeared to switch from 'growth inhibitory' in acutely-treated cells to 'pro-survival' in chronically-adapted cells. Cetuximab treatment appeared to negatively select initially dominant IFN-sensitive clones and promoted selection of IFN- and cetuximab-refractory tumor clones constitutively bearing an up-regulated IFN/STAT1 signaling. High-levels of mRNAs coding for the EGFR ligands amphiregulin (AREG), epiregulin (EREG), and neuregulin-1/heregulin (NRG1) predicted for acute cetuximab's functioning. Chronic cetuximab, however, appeared to negatively select initially dominant AREG/EREG/NRG1-positive clones to promote selection of cetuximab-refractory clones exhibiting a knocked-down neuregulin signaling. Our current evolutionary mapping of the transcriptomic changes that occur during cetuximab-induced chronic blockade of EGFR/KRAS WT signaling strongly suggests that mRNAs coding for IFN/STAT1- and EGFR ligands-related genes can be evaluated as novel predictors of efficacy in KRAS WT squamous cancer patients being treated with cetuximab.
Filtering Schilling manipulator commands to prevent flexible structure vibration (2005)

The remediation and management of various nuclear sites will require inspection, removal and surveillance operations within many waste storage tanks. Due to the large dimensions, many tasks will be performed with a small articulated robot mounted on a long reach manipulator. However, the motion of the small arm tends to excite the vibrational modes of the larger structure. This paper presents several applications of a finite impulse response (FIR) compensation filter within the micromanipulator's joint feedback control structure to suppress the structure's flexible behavior. Simulation results of filtering a Schilling manipulator's azimuth joint commands while mounted on the tip of a long slender beam verify the effectiveness of the proposed control strategies.
TEMPO 3.1: A Body Area Sensor Network Platform for Continuous Movement Assessment (2009)

This work presents TEMPO (Technology-Enabled Medical Precision Observation) 3.1, a third generation body area sensor platform that accurately and precisely captures, processes, and wirelessly transmits six-degrees-of-freedom inertial data in a wearable, non-invasive form factor. TEMPO 3.1 is designed to be usable to both the wearer and researcher, thereby enabling motion capture applications in body area sensor networks (BASNs). A complete system is designed and developed that includes the following: (1) enabling technologies and hardware designof TEMPO 3.1, (2) a custom real-time operating system (TEMPOS) that manages all aspects of signal acquisition, signal processing, data management, peripheral control, and wireless communication on a TEMPO node, and (3) a custom case design. The system is evaluated and compared to existing BASN hardware platforms. TEMPO 3.1 creates new opportunities for wearable, continuous monitoring applications and extends the research space of current efforts.
Purification of human erythroid colony-forming units and demonstration of specific binding of erythropoietin. (1987)

Morphological and biochemical studies of human colony-forming units-erythroid (CFU-E) have been hindered by their extreme rarity. Since burst-forming units-erythroid (BFU-E) develop into CFU-E, we used normal human blood BFU-E to generate large numbers of highly purified CFU-E in vitro. Using density centrifugation, sheep erythrocyte rosetting, surface immunoglobulin-positive cell depletion, adherence to plastic, and negative panning with monoclonal antibodies, human blood BFU-E were purified from 0.017 to 0.368%, a 22-fold purification with a 43% yield. The panned cells were cultured in methylcellulose with recombinant erythropoietin (rEp) and conditioned medium for 9 d. These cells were then collected and CFU-E were further purified using adherence and density centrifugation. This yielded almost 10(7) erythroid colony forming cells with a purity of 70 +/- 18%. Analysis of these cells by light and electron microscopy showed 94% erythroid cells. The prominent cell was a primitive blast with high nuclear/cytoplasmic ratio, dispersed nuclear chromatin and a distinct large nucleolus. The relation between the number of erythroid colonies and the number of day 9 cells plated in plasma clots was a straight line through the origin with a maximum number of erythroid colonies at 1 U/ml of rEp and no erythroid colonies without rEp. Specific binding with 125I-rEp showed that 60% of the binding was inhibited by excess pure erythropoietin (Ep), but not by albumin, fetal calf serum, and a variety of growth factors or glycoproteins. By days 12-13 of cell culture, when the progenitor cells matured to late erythroblasts, specific binding markedly declined. In this study, human CFU-E have been isolated in sufficient purity to characterize the morphology of these rare cells and in sufficient numbers to measure specific binding of Ep.
Anaphora resolution in slot grammar (1990)

We present three algorithms for resolving anaphora in Slot Grammar: (1) an algorithm for interpreting elliptical VPs in antecedent-contained deletion structures, subdeletion constructions, and intersentential cases; (2) a syntactic filter on pronominal coreference; and (3) an algorithm for identifying the binder of an anaphor (reflexive pronoun or the reciprocal phrase other). These algorithms operate on the output of a Slot Grammar parser, and, like the parser, they run in Prolog. The VP anaphora algorithm implements an S-structure analysis of VP ellipsis that we argue provides a more unified and empirically motivated treatment of VP anaphora resolution than analyses that attempt to interpret elliptical VPs at a level of logical form. Each algorithm can operate independently of the others, and we have incorporated each into an integrated anaphora resolution component. The interpreted elliptical VP structures that the VP anaphora algorithm produces provide the input to the two NP anaphora resolution procedures. The integrated anaphora resolution component provides a powerful syntactically driven module for generating partially interpreted representations that can serve as input to semantic and discourse interpretation systems.
Psoralen covalently linked to oligodeoxyribonucleotides: synthesis, sequence specific recognition of DNA and photo-cross-linking to pyrimidine residues of DNA (1989)

The psoralen derivative 4,5',8-trimethylpsoralen was covalently linked to the 5'-terminus of an 18mer oligodeoxyribonucleotide in the course of solid phase synthesis using phosphoroamidite chemistry. The derivative was introduced as a phosphitylation compound in the last cycle of the oligomer synthesis. The reagent was prepared by 4'-chloromethylation of 4,5',8-trimethylpsoralen, introduction of a linker by ethanediol and phosphitylation with chloro-[(beta-cyanoethoxy)-N,N-diisopropylamino]-phosphine. After oxydation and deprotection the 5'-psoralen modified oligodeoxyribonucleotide was characterised by HPLC. Hybridisation of the psoralen-modified oligomer to a complementary single stranded 21mer followed by irradiation at 350 nm revealed a photo-cross-linked double-stranded DNA fragment analysed on denaturing polyacrylamide gels. The cross-link could be reversed upon irradiation at 254nm.
The First Suzuki Cross-Couplings of Aryltrimethylammonium Salts (2003)

The first Suzuki cross-coupling reaction of aryltrimethylammonium triflates based on the use of an IMes.Ni(0) catalyst system is described. A wide range of electron-withdrawing and electron-donating substituents are tolerated on both the aryltrimethylammonium triflate and the boronic acid components of this reaction. In addition to arylboronic acids, the scope of the reaction is extended to encompass both boronate esters and alkenylboranes. This methodology constitutes a novel, mild method to activate anilines for metal-catalyzed cross-coupling reactions.
Constituents of the Essential Oil ofSuregada zanzibariensisLeaves are Repellent to the Mosquito,Anopheles gambiaes.s. (2010)

In traditional African communities, repellent volatiles from certain plants generated by direct burning or by thermal expulsion have played an important role in protecting households against vectors of malaria and other diseases. Previous research on volatile constituents of plants has shown that some are good sources of potent mosquito repellents. In this bioprospecting initiative, the essential oil of leaves of the tree, Suregada zanzibariensis Verdc. (Angiospermae: Euphobiaceae) was tested against the mosquito, Anopheles gambiae s.s. Giles (Diptera: Culicidae) and found to be repellent. Gas chromatography (GC), GC-linked mass spectrometry (GC-MS) and, where possible, GC-co-injections with authentic compounds, led to the identification of about 34 compounds in the essential oil. About 56% of the constituents were terpenoid ketones, mostly methyl ketones. Phenylacetaldehyde (14.4%), artemisia ketone (10.1%), (1S)-(-)-verbenone (12.1%) and geranyl acetone (9.4%) were the main constituents. Apart from phenylacetaldehyde, repellent activities of the other main constituents were higher than that of the essential oil. The blends of the main constituents in proportions found in the essential oil were more repellent to An. gambiae s.s. than was the parent oil (p < 0.05), and the presence of artemisia ketone in the blend caused a significant increase in the repellency of the resulting blend. These results suggested that blends of some terpenoid ketones can serve as effective An. gambiae s.s. mosquito repellents.
PHDs overactivation during chronic hypoxia “desensitizes” HIFα and protects cells from necrosis (2008)

Cell adaptation to changes in oxygen (O(2)) availability is controlled by two subfamilies of O(2)-dependent enzymes: the hypoxia inducible factor (HIF)-prolyl and asparaginyl hydroxylases [prolyl hydroxylases domain (PHDs) and factor inhibiting HIF (FIH)]. These oxygen sensors regulate the activity of the HIF, a transcriptional complex central in O(2) homeostasis. In well oxygenated cells, PHDs hydroxylate the HIFalpha subunits, thereby targeting them for proteasomal degradation. In contrast, acute hypoxia inhibits PHDs, leading to HIFalpha stabilisation. However, here we show that chronic hypoxia induces HIF1/2alpha"desensitization" in cellulo and in mice. At the basis of this general adaptative mechanism, we demonstrate that chronic hypoxia not only increases the pool of PHDs but also overactivates the three PHD isoforms. This overactivation appears to be mediated by an increase in intracellular O(2) availability consequent to the inhibition of mitochondrial respiration. By using in cellulo and in vivo siRNA, we found that the PHDs are the key enzymes triggering HIFalpha desensitization, a feedback mechanism required to protect cells against necrotic cell death and thus to adapt them across a chronic hypoxia. Hence, PHDs serve as dual enzymes, for which inactivation and later overactivation is necessary for cell survival in acute or chronic hypoxia, respectively.
NF‐κB and estrogen receptor α interactions: Differential function in estrogen receptor‐negative and ‐positive hormone‐independent breast cancer cells (2009)

Estrogen receptor (ER)-positive breast cancer cells have low levels of constitutive NF-kappaB activity while ER negative (-) cells and hormone-independent cells have relatively high constitutive levels of NF-kappaB activity. In this study, we have examined the aspects of mutual repression between the ERalpha and NF-kappaB proteins in ER+ and ER- hormone-independent cells. Ectopic expression of the ERalpha reduced cell numbers in ER+ and ER- breast cancer cell lines while NF-kappaB-binding activity and the expression of several NF-kappaB-regulated proteins were reduced in ER- cells. ER overexpression in ER+/E2-independent LCC1 cells only weakly inhibited the predominant p50 NF-kappaB. GST-ERalpha fusion protein pull downs and in vivo co-immunoprecipitations of NF-kappaB:ERalpha complexes showed that the ERalpha interacts with p50 and p65 in vitro and in vivo. Inhibition of NF-kappaB increased the expression of diverse E2-regulated proteins. p50 differentially associated directly with the ER:ERE complex in LCC1 and MCF-7 cells by supershift analysis while p65 antibody reduced ERalpha:ERE complexes in the absence of a supershift. ChIP analysis demonstrated that NF-kappaB proteins are present on an endogenous ERE. Together these results demonstrate that the ER and NF-kappaB undergo mutual repression, which may explain, in part, why expression of the ERalpha in ER- cells does not confer growth signaling. Secondly, the acquisition of E2-independence in ER+ cells is associated with predominantly p50:p50 NF-kappaB, which may reflect alterations in the ER in these cells. Since the p50 homodimer is less sensitive to the presence of the ER, this may allow for the activation of both pathways in the same cell.
Fiber optic fluid detector (2023)

Particular gases or liquids are detected with a fiber optic element (11, 11a to 11j) having a cladding or coating of a material (23, 23a to 23j) which absorbs the fluid or fluids and which exhibits a change of an optical property, such as index of refraction, light transmissiveness or fluoresence emission, for example, in response to absorption of the fluid. The fluid is sensed by directing light into the fiber optic element and detecting changes in the light, such as exit angle changes for example, that result from the changed optical property of the coating material. The fluid detector (24, 24a to 24j) may be used for such purposes as sensing toxic or explosive gases in the atmosphere, measuring ground water contamination or monitoring fluid flows in industrial processes, among other uses.
Case Definitions of Clinical Malaria under Different Transmission Conditions in Kilifi District, Kenya (2005)

Case definitions of malaria are bound to be altered by factors that affect immunity, such as age and transmission. Case definitions may, however, be affected by other immunity-altering factors, such as HIV and vaccination status, and this needs to be borne in mind during vaccine trials.
Local Perfusion of the Tumor Necrosis Factor α Blocker Infliximab to the Inner Ear Improves Autoimmune Neurosensory Hearing Loss (2006)

The results of this pilot trial demonstrate that in patients with AIED, transtympanic delivery of the TNF-alpha blocker infliximab once weekly for 4 weeks allowed steroids to be tapered off, resulted in hearing improvement and reduced disease relapses. These preliminary efficacy and safety results appear encouraging enough to warrant further follow-up and studies for better determination of the potential clinical utility of local administration of infliximab for autoimmune hearing loss.
Structure of carbohydrate units of ovine luteinizing hormone. (1982)

The detailed structures of the three asparagine-linked carbohydrate units of ovine lutropin subunits alpha and beta (oLH-alpha and oLH-beta) have been determined by carrying out the structural analysis on the three glycopeptides alpha GP-1, alpha GP-2, and beta GP-3, and the oligosaccharide obtained by alkaline sodium borohydride treatment of oLH and the individual subunits. Based on the results of methylation, periodate oxidation, deamination, acetolysis, and enzymatic studies with exoglycosidases, the following structure is proposed for the carbohydrate units of oLH. Methylation studies indicated that the 3 N-acetylglucosaminyl residues were substituted at 1-, 1,4-, and 1,4,6-positions. Two of the three mannosyl residues were 1,2-linked and 3rd mannosyl residue was 1,3,6-linked. Fucose and galactose were terminally located and N-acetylgalactosamine was substituted at C-4. Periodate oxidation studies were consistent with the methylation data. The isolation of (formula, see text) 2,5-anhydromannose by the deamination of the oLH oligosaccharide established the branched structure for the mannosyl residues as well as the linkage of the trimannose unit to N-acetylglucosamine. The nonreducing terminal position of N-acetylgalactosamine was indicated by the formation of N-acetylgalactosaminyl glyceraldehyde on Smith degradation of oLH. The presence of a substituent "X" on N-acetylgalactosamine was established by the isolation of X-2,5-anhydrotalitol from the deamination products of oLH oligosaccharide. X was found to be an acid-labile substituent and was identified as a sulfate ester. Last but not least, since oLH oligosaccharide, obtained by hydrolysis of the hormone with NaOH + NaBH4, contained N-acetylglucosaminitol at the reducing end, the carbohydrate must be linked to the protein through N-acetylglucosamine.
PD-1 and Its Ligands in Tolerance and Immunity (2008)

Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential.
A new method for accurate assessment of DNA quality after bisulfite treatment (2007)

The covalent addition of methylgroups to cytosine has become the most intensively researched epigenetic DNA marker. The vast majority of technologies used for DNA methylation analysis rely on a chemical reaction, the so-called 'bisulfite treatment', which introduces methylation-dependent sequence changes through selective chemical conversion of non-methylated cytosine to uracil. After treatment, all non-methylated cytosine bases are converted to uracil but all methylated cytosine bases remain cytosine. These methylation dependent C-to-T changes can subsequently be studied using conventional DNA analysis technologies. The bisulfite conversion protocol is susceptible to processing errors, and small deviation from the protocol can result in failure of the treatment. Several attempts have been made to simplify the procedure and increase its robustness. Although significant achievements in this area have been made, bisulfite treatment remains the main source of process variability in the analysis of DNA methylation. This variability in particular impairs assays, which strive for the quantitative assessment of DNA methylation. Here we present basic mathematical considerations, which should be taken into account when analyzing DNA methylation. We also introduce a PCR-based assay, which allows ab initio assessment of the DNA quality after bisulfite treatment and can help to prevent inaccurate quantitative measurement resulting from poor bisulfite treatment.
Reductive Electron Injection into Duplex DNA by Aromatic Amines (2004)

An assay based on photoinduced reaction and subsequent cleavage of duplex DNA containing a bromodeoxyuridine ((Br)U) residue and an abasic site was developed to screen aromatic amines for their ability to initiate charge transfer by reductive electron donation. Two candidates, N,N,N',N'-tetramethyl-1,5-diaminonaphthalene (TMDN) and 1,5-diaminonaphthalene (DAN), expressed the desired activity, and an oligodeoxynucleotide-TMDN conjugate was subsequently prepared to identify additional variables affecting the efficiency of electron injection and transfer into DNA. This system demonstrated only mild sensitivity to molecular oxygen but was strongly inhibited by high concentrations of 2-mercaptoethanol. The nucleobase counter to the attached TMDN strongly modulated charge transfer as evident by a 60-fold decrease in reduction of the distal (Br)U when the counterbase A was substituted for C. An inverse relationship between this reduction and quenching of TMDN fluorescence by the counterbase was also discovered and is consistent with a competition between radical recombination and electron migration away from the initial site of its injection into DNA.
Histidine-41 of the Cytochrome b 5Domain of the Borage Δ6 Fatty Acid Desaturase Is Essential for Enzyme Activity (1999)

Unlike most other plant microsomal desaturases, the Delta6-fatty acid desaturase from borage (Borago officinalis) contains an N-terminal extension that shows homology to the small hemoprotein cytochrome (Cyt) b5. To determine if this domain serves as a functional electron donor for the Delta6-fatty acid desaturase, mutagenesis and functional analysis by expression in transgenic Arabidopsis was carried out. Although expression of the wild-type borage Delta6-fatty acid desaturase resulted in the synthesis and accumulation of Delta6-unsaturated fatty acids, this was not observed in plants transformed with N-terminally deleted forms of the desaturase. Site-directed mutagenesis was used to disrupt one of the axial heme-binding residues (histidine-41) of the Cyt b5 domain; expression of this mutant form of the Delta6-desaturase in transgenic plants failed to produce Delta6-unsaturated fatty acids. These data indicate that the Cyt b5 domain of the borage Delta6-fatty acid desaturase is essential for enzymatic activity.
Effect of Glucagon on Food Intake and Body Weight in Man (1957)

A series of 10 patients was studied for a 5-week period to note the effect of glucagon on food intake and body weight. The first week was spent in learning their food preferences and judging the usual range of intake. This was followed by two periods, each of 2 weeks' duration during which the drugs were administered. Glucagon was administered for one of these two periods. The dose was 1 mg administered intramuscularly 10 minutes prior to each meal. A placebo solution was administered in an identical manner during the other period. The study was performed in a completely ‘blind’ manner. There was a highly significant diminution in caloric intake while receiving glucagon. The average difference in daily caloric intake was 440 calories. The difference in weight for the two experimental periods was also significant. Submitted on June 16, 1957