gebhart/patrepeval huggingface dataset:
Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia (2015)

Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in genes encoding epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable, with few means to predict which patients will benefit. Here, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients who were responsive or resistant to decitabine (DAC) in order to develop a molecular means of predicting response at diagnosis. While somatic mutations did not differentiate responders from nonresponders, we identified 167 differentially methylated regions (DMRs) of DNA at baseline that distinguished responders from nonresponders using next-generation sequencing. These DMRs were primarily localized to nonpromoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. Transcriptional analysis revealed differences in gene expression at diagnosis between responders and nonresponders. In responders, the upregulated genes included those that are associated with the cell cycle, potentially contributing to effective DAC incorporation. Treatment with CXCL4 and CXCL7, which were overexpressed in nonresponders, blocked DAC effects in isolated normal CD34+ and primary CMML cells, suggesting that their upregulation contributes to primary DAC resistance.
The selectivity of protein kinase inhibitors: a further update (2007)

The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information, the effects of compounds that we have studied in cells and other data in the literature, we recommend the use of the following small-molecule inhibitors: SB 203580/SB202190 and BIRB 0796 to be used in parallel to assess the physiological roles of p38 MAPK (mitogen-activated protein kinase) isoforms, PI-103 and wortmannin to be used in parallel to inhibit phosphatidylinositol (phosphoinositide) 3-kinases, PP1 or PP2 to be used in parallel with Src-I1 (Src inhibitor-1) to inhibit Src family members; PD 184352 or PD 0325901 to inhibit MKK1 (MAPK kinase-1) or MKK1 plus MKK5, Akt-I-1/2 to inhibit the activation of PKB (protein kinase B/Akt), rapamycin to inhibit TORC1 [mTOR (mammalian target of rapamycin)-raptor (regulatory associated protein of mTOR) complex], CT 99021 to inhibit GSK3 (glycogen synthase kinase 3), BI-D1870 and SL0101 or FMK (fluoromethylketone) to be used in parallel to inhibit RSK (ribosomal S6 kinase), D4476 to inhibit CK1 (casein kinase 1), VX680 to inhibit Aurora kinases, and roscovitine as a pan-CDK (cyclin-dependent kinase) inhibitor. We have also identified harmine as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro. The results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes.
Photonic ADC: overcoming the bottleneck of electronic jitter (2012)

Accurate conversion of wideband multi-GHz analog signals into the digital domain has long been a target of analog-to-digital converter (ADC) developers, driven by applications in radar systems, software radio, medical imaging, and communication systems. Aperture jitter has been a major bottleneck on the way towards higher speeds and better accuracy. Photonic ADCs, which perform sampling using ultra-stable optical pulse trains generated by mode-locked lasers, have been investigated for many years as a promising approach to overcome the jitter problem and bring ADC performance to new levels. This work demonstrates that the photonic approach can deliver on its promise by digitizing a 41 GHz signal with 7.0 effective bits using a photonic ADC built from discrete components. This accuracy corresponds to a timing jitter of 15 fs - a 4-5 times improvement over the performance of the best electronic ADCs which exist today. On the way towards an integrated photonic ADC, a silicon photonic chip with core photonic components was fabricated and used to digitize a 10 GHz signal with 3.5 effective bits. In these experiments, two wavelength channels were implemented, providing the overall sampling rate of 2.1 GSa/s. To show that photonic ADCs with larger channel counts are possible, a dual 20-channel silicon filter bank has been demonstrated.
Ribonucleic acid synthesis after adsorption of the bacteriophage lambda on Escherichia coli minicells. (1975)

Lambda bacteriophage adsorbs on the chromosome-less small bodies (minicells) produced by aberrant cell division of Escherichia coli P678-54. The plasmid-less minicells, as well as the minicells harbouring the colicinogenic factor E1, reveal a considerable inhibition of total RNA synthesis after phage adsorption. Both kinds of minicells synthesize RNA hybridizable to lambda DNA, but in the plasmid-harbouring minicells lambda RNA synthesis is much more intensive.
Pharmacokinetics of Novel Erythropoiesis Stimulating Protein Compared with Epoetin Alfa in Dialysis Patients (1999)

Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (Epoetin) which has an increased terminal half-life in animal models. The aim of this study was to extend these observations to humans. Using a double-blind, randomized, cross-over design, the single-dose pharmacokinetics of Epoetin alfa (100 U/kg) and an equivalent peptide mass of NESP were compared following intravenous bolus in 11 stable peritoneal dialysis patients. This was followed by an open-label study to determine the single-dose pharmacokinetics of an equivalent peptide mass of NESP by subcutaneous injection in six of these patients. The mean terminal half-life for intravenous NESP was threefold longer than for intravenous Epoetin (25.3 versus 8.5 h), a difference of 16.8 h (95% confidence interval, 9.4 to 24.2 h, P = 0.0008). The area under the serum concentration-time curve was significantly greater for NESP (291.0 +/- 7.6 ng x h per ml versus 131.9 +/- 8.3 ng x h per ml; mean +/- SEM; P < 0.0005), and clearance was significantly lower (1.6 +/- 0.3 ml/h per kg versus 4.0 +/- 0.3 ml/h per kg; mean +/- SEM; P < 0.0005). The volume of distribution was similar for NESP and Epoetin (52.4 +/- 2.0 ml/kg versus 48.7 +/-2.1 ml/kg; mean +/-SEM). The mean terminal half-life for subcutaneous NESP was 48.8 h. The peak concentration of subcutaneous NESP was approximately 10% of that following intravenous administration, and bioavailability was approximately 37% by the subcutaneous route. The longer half-life of NESP is likely to confer a clinical advantage over Epoetin by allowing less frequent dosing in patients treated for anemia.
Long Germanium Nanowires Prepared by Electrochemical Etching (2006)

Germanium (Ge) nanowires have been produced by electrochemical etching of single-crystalline n-type Ge [100] in a HCl-containing aqueous electrolyte. Macropores could be etched at various etching currents after an optimized procedure for homogeneous pore nucleation was used. Because of the narrow band gap of Ge (0.66 eV), the leakage current through pore walls is much higher than that, for example, in Si, leading to a constant dissolution of the pore walls. At sufficiently high current densities, it is then possible to form nanowires with diameters determined by the width of the space charge region, ranging from roughly 50 to 500 nm, and a length of several hundred micrometers. The role of the space charge region for stabilizing pore formation and in the formation of nanowires will be discussed.
Functional Blockade of Platelet-Derived Growth Factor Receptor-β but Not of Receptor-α Prevents Vascular Smooth Muscle Cell Accumulation in Fibrous Cap Lesions in Apolipoprotein E–Deficient Mice (2001)

These results indicate that PDGFR-beta plays a significant role in formation of fibrous atherosclerotic lesions and that regulation of the signal transduction through PDGFR-beta could affect atherogenesis in mice.
Hybridization of Alternating Cationic/Anionic Oligonucleotides to RNA Segments (1994)

Abstract It is shown that oligonucleotide analogues containing alternating phosphodiester groups and cationic groups linked to phosphorus through an amidate bond hybridize to complementary RNA segments. An improved synthetic procedure for the alternating compounds is also described.
Topography of the high-affinity lysine binding site of plasminogen as defined with a specific antibody probe (1986)

An antibody population that reacted with the high-affinity lysine binding site of human plasminogen was elicited by immunizing rabbits with an elastase degradation product containing kringles 1-3 (EDP I). This antibody was immunopurified by affinity chromatography on plasminogen-Sepharose and elution with 0.2 M 6-aminohexanoic acid. The eluted antibodies bound [125I]EDP I, [125I]Glu-plasminogen, and [125I]Lys-plasminogen in radioimmunoassays, and binding of each ligand was at least 99% inhibited by 0.2 M 6-aminohexanoic acid. The concentrations for 50% inhibition of [125I]EDP I binding by tranexamic acid, 6-aminohexanoic acid, and lysine were 2.6, 46, and 1730 microM, respectively. Similar values were obtained with plasminogen and suggested that an unoccupied high-affinity lysine binding site was required for antibody recognition. The antiserum reacted exclusively with plasminogen derivatives containing the EDP I region (EDP I, Glu-plasminogen, Lys-plasminogen, and the plasmin heavy chain) and did not react with those lacking an EDP I region [miniplasminogen, the plasmin light chain or EDP II (kringle 4)] or with tissue plasminogen activator or prothrombin, which also contain kringles. By immunoblotting analyses, a chymotryptic degradation product of Mr 20,000 was derived from EDP I that retained reactivity with the antibody. The high-affinity lysine binding site was equally available to the antibody probe in Glu- and Lys-plasminogen and also appeared to be unoccupied in the plasmin-alpha 2-antiplasmin complex. alpha 2-Antiplasmin inhibited the binding of radiolabeled EDP I, Glu-plasminogen, or Lys-plasminogen by the antiserum, suggesting that the recognized site is involved in the noncovalent interaction of the inhibitor with plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS)
Prototyping orientation and motion sensing objects with open hardware (2013)

This studio aims to introduce participants to orientation and motion sensing based upon inertial, magnetic and atmospheric pressure MEMS sensors. By using two Open Hardware projects we developed, FreeIMU and LibreMote, through hands on experimentation, participants will discover the capabilities and limits of current MEMS accelerometers, gyroscopes, magnetometers and barometers, the basics and state of the art of sensor fusion algorithms and the challenges of calibration.
Biosensor Analysis of the Interaction between Immobilized Human Serum Albumin and Drug Compounds for Prediction of Human Serum Albumin Binding Levels (2000)

The interactions between a set of drugs, selected on the basis of reported human serum albumin (HSA) binding levels, and immobilized HSA were investigated using surface plasmon resonance technology. Major HSA binding sites were available after immobilization. The intensity of the signal obtained from the interaction of the drug with the HSA surface was correlated with the reported HSA binding level. Drugs were classified into groups corresponding to high, medium, or low HSA binding based on the injection of the drug at 80 microM concentration. A set of 10 drugs binding to alpha(1)-acid glycoprotein (AGP) was also investigated and correlated with reported AGP binding data. The throughput of the presented assay is 100 compounds/24 h, and the sample consumption is less than 100 microL (8 nmol).
Photographic tone reproduction for digital images (2002)

A classic photographic task is the mapping of the potentially high dynamic range of real world luminances to the low dynamic range of the photographic print. This tone reproduction problem is also faced by computer graphics practitioners who map digital images to a low dynamic range print or screen. The work presented in this paper leverages the time-tested techniques of photographic practice to develop a new tone reproduction operator. In particular, we use and extend the techniques developed by Ansel Adams to deal with digital images. The resulting algorithm is simple and produces good results for a wide variety of images.
Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn’s disease (2008)

It is not until severe UC that there is a global change in mucosal protection as a consequence of large regions lacking mucus, a decrease in secretory potential caused by a loss of goblet cells and a thinner, less effective mucus layer even when it is present.
Extracting Tree-Structured Representations of Trained Networks (1995)

A significant limitation of neural networks is that the representations they learn are usually incomprehensible to humans. We present a novel algorithm, TREPAN, for extracting comprehensible, symbolic representations from trained neural networks. Our algorithm uses queries to induce a decision tree that approximates the concept represented by a given network. Our experiments demonstrate that TREPAN is able to produce decision trees that maintain a high level of fidelity to their respective networks while being comprehensible and accurate. Unlike previous work in this area, our algorithm is general in its applicability and scales well to large networks and problems with high-dimensional input spaces.
Nanoshell-Enabled Photonics-Based Imaging and Therapy of Cancer (2004)

Metal nanoshells are a novel type of composite spherical nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) wavelength region where tissue transmissivity peaks. In addition to spectral tunability, nanoshells offer other advantages over conventional organic dyes including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. In this article, we first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.
An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells (2016)

Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells.
A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity (2000)

The A1555 G mutation in mitochondrial 12S rRNA has been found to be associated with non-syndromic deafness and aminoglycoside-induced deafness. The sensitivity to the aminoglycoside paromomycin has been analyzed in lymphoblastoid cell lines derived from five deaf individuals and five hearing individuals from an Arab-Israeli family carrying the A1555G mutation, and three married-in controls from the same family. Exposure to a high concentration of paromomycin (2 mg/ml), which caused an 8% average increase in doubling time (DT) in the control cell lines, produced higher average DT increases (49 and 47%) in the A1555G mutation-carrying cell lines derived from symptomatic and asymptomatic individuals, respectively. The ratios of translation rates in the presence and absence of paromomycin, which reflected the effect of the drug on mitochondrial protein synthesis, were significantly decreased in the cell lines derived from symptomatic and asymptomatic individuals (by 30 and 28% on average, respectively), compared with the ratios in the control cell lines. These ratios showed, in both groups of mutant cell lines, a significant negative correlation with the ratios of DTs in the presence and absence of the antibiotic. These results have provided the first direct evidence that the mitochondrial 12S rRNA carrying the A1555G mutation is the main target of aminoglycosides. They suggest that these antibiotics exert their detrimental effect through an alteration of mitochondrial protein synthesis, which exacerbates the inherent defect caused by the mutation, reducing the overall translation rate down to and below the minimal level required for normal cellular function (40-50%).
Lipoxin A4 Stable Analogs Are Potent Mimetics That Stimulate Human Monocytes and THP-1 Cells via a G-protein-linked Lipoxin A4 Receptor (1997)

Lipoxins (LX) are bioactive eicosanoids that activate human monocytes and inhibit neutrophils. LXA4 is rapidly converted by monocytes to inactive products, and to resist metabolism, synthetic analogs of LXA4 were designed. Here, we examined the bioactivity of several LXA4 analogs in monocytes and found, for chemotaxis, 15(R/S)-methyl-LXA4 and 15-epi-LXA4 were equal in activity, and 16-phenoxy-LXA4 was more potent than native LXA4. Both 15(R/S)-methyl-LXA4 and 16-phenoxy-LXA4 were approximately 1 log molar more potent than LXA4 in stimulating THP-1 cell adherence (EC50 approximately 1 x 10(-10) M). Dimethylamide derivatives of the LXA4 analogs also possessed agonist rather than antagonist properties for monocytes. Neither LXA4 nor 16-phenoxy-LXA4 affected monocyte-mediated cytotoxicity. We cloned an LXA4 receptor from THP-1 cells identical to that found in PMN. Evidence of receptor-mediated function of LXA4 and the stable analogs in monocytes included desensitization of intracellular calcium mobilization to a second challenge by equimolar concentrations of these analogs, but not to LTB4. Increases in [Ca2+]i by LXA4 and the analogs were specifically inhibited by an antipeptide antibody to the LXA4 receptor; and both LXA4- and analog-induced adherence and increments in Ca2+ were sensitive to pertussis toxin. Together, these results indicate that the LXA4 stable analogs are potent monocyte chemoattractants and are more potent than native LXA4 in stimulating THP-1 cell adherence, at subnanomolar concentrations. Moreover, they provide additional evidence that the LXA4 stable analogs retain selective bioactivity in monocytes and are valuable instruments for examining the functions and modes of action of LXA4.
Risk Indicators for HIV-Associated Jointly Occurring Oral Candidiasis and Oral Hairy Leukoplakia (2007)

Joint occurrence of two or more diseases may impact their transmission, clinical presentation, management approaches, and treatment efficacy. Although oral candidiasis (OC) and oral hairy leukoplakia (OHL) are the most commonly occurring opportunistic oral diseases of HIV-infected patients, literature describing their joint occurrence is sparse. The purpose of this project was to develop an explanatory multivariable model for joint occurrence of OC and OHL (OC-OHL). This cross-sectional study examined 631 adult dentate HIV-1 seropositive persons for OC and OHL from 1995-2000 at the University of North Carolina Hospitals in Chapel Hill, NC. Data collected from medical record review, interviews and clinical examinations were analyzed using chi(2) tests, t itests, and nonparametric tests. Multivariable proportional odds models were developed, using the likelihood ratio test and adjusting for several demographic, behavioral, and biological factors. Thirteen percent of participants had OC only; 12.8% had OHL only; 4.6% had OC-OHL; whereas 69.7% had neither. Occurrence of OC-OHL was independently associated with CD4+ counts less than 200 cells per microliter (adjusted odds ratio [OR] (95% confidence interval {CI}) = 13.4 (6.6, 27.2) and CD4+ counts 200-499 cells per microliter (OR = 3.9 [1.9, 8.1]); current smokers (OR = 2.3 [1.4, 3.8]); and whites (OR = 1.7 [1.1, 2.5]). Combination antiretroviral therapy was protective (OR = 0.5 [0.3, 0.9]). In an HIV-1-infected population, lower CD4+ cell counts and smoking were important independent risk indicators for joint occurrence of OC and OHL.