gebhart/patrepeval huggingface dataset:
Cancer Stem Cells (2006)

Researchers have made stunning advances over the last fifty years in characterizing the oncogenic mutations that lead to cancer. However, we are just beginning to understand the complex consequences of these mutations and how they result in neoplastic transformation at the cellular level. Most cancers arise in tissues that contain a stem cell population, such as gut, breast, prostate, lung, and bone marrow. Stem cells are defined by three critical properties: the ability to divide and give rise to a new stem cell (self-renewal), the ability to give rise to the differentiated cells of an organ, and the genetic constraints on expansion of the cell population. It is known that cancer results from the accumulation of mutations in a single target cell, sometimes over a period of many years. Since stem cells are the only long-lived cells in most tissues, this suggests that they are the cells in which early mutations leading to cancer accumulate. Additionally, stem cells are the only normal cells that share cancer cells' intrinsic ability to self-renew. Taken together, these two facts suggest that, in some cases, stem cells may be the target cells for neoplastic transformation. Presently, therapeutic targets are selected on the basis of the assumption that all of the cancer cells within a particular tumor are equivalent in that they are all capable of driving tumorigenesis and metastasis. New data suggests that, in at least some cancers, a small, phenotypically distinct subset of the cancer cells (tumorigenic cells, or cancer stem cells) has the exclusive ability to form tumors. The rest of the cells, which form the bulk of the tumor, are unable to self-renew or sustain tumorigenesis. Tumorigenic and nontumorigenic cancer cells can be identified on the basis of cell surface-marker expression, utilizing the same tools used in normal stem cell biology. This suggests that therapies could be made more effective by targeting the tumorigenic cell population. The ability to identify tumorigenic cancer cells should therefore allow the identification of new diagnostic markers and therapeutic targets, better evaluation of candidate therapeutics, and more accurate determination of therapeutic efficacy.
A total internal‐reflection technique for the examination of protein adsorption (1977)

A total internal-reflection fluorescence (TIRF) technique for examining protein adsorption at solid-liquid interfaces is described. For the representative case of adsorption of bovine gamma-globulin onto silicone rubber, the applicability of the technique to serveral important aspects of protein adsorption phenomena is demonstrated. Specifically, in addition to the tightly adsorbed protein layer observed herein and previously by maany others, the presence of a loosely adsorbed protein layer was also noted under conditions of either static or flowing protein solutions. Taking advantage of the continuous real-time measurements possible with TIRF, a rate constant for the protein adsorption step during laminar flow was estimated at both 25 and 37 degrees C. These results serve to demonstrate that the TIRF technique represents a significant and versatile new tool for the study of protein adsorption phenomena.
Hypertonic Stress Increases T Cell Interleukin-2 Expression through a Mechanism That Involves ATP Release, P2 Receptor, and p38 MAPK Activation (2003)

Hypertonic stress (HS) can alter the function of mammalian cells. We have reported that HS enhances differentiated responses of T cells by increasing their ability to produce interleukin (IL)-2, a finding of clinical interest because hypertonic infusions may modulate immune function in patients. HS shrinks cells and mechanically deforms membranes, which results in ATP release from many cell types. Here we investigate if ATP release is an underlying mechanism through which HS augments T cell function. We found that mechanical stress and HS induced rapid ATP release from Jurkat T cells. HS and exogenous ATP mobilized intracellular Ca(2+), activated p38 MAPK, and increased IL-2 expression. Ca(2+) mobilization was attenuated in the presence of EGTA or by removal of extracellular ATP with apyrase. Adenosine did not increase IL-2 expression, as did ATP. Apyrase, inhibition of P2 receptors, or inhibition of p38 MAPK with SB203580 reduced the stimulatory effects of HS, indicating that HS enhances IL-2 expression through a mechanism that involves ATP release, P2 (perhaps P2X7) receptors, and p38 MAPK activation. We conclude that release of and response to ATP plays a key role in the mechanism through which hypertonic stress regulates the function of T cells.
Novel Human Monoclonal Antibody Combination Effectively Neutralizing Natural Rabies Virus Variants and Individual In Vitro Escape Mutants (2005)

The need to replace rabies immune globulin (RIG) as an essential component of rabies postexposure prophylaxis is widely acknowledged. We set out to discover a unique combination of human monoclonal antibodies (MAbs) able to replace RIG. Stringent criteria concerning neutralizing potency, affinity, breadth of neutralization, and coverage of natural rabies virus (RV) isolates and in vitro escape mutants were set for each individual antibody, and the complementarities of the two MAbs were defined at the onset. First, we identified and characterized one human MAb (CR57) with high in vitro and in vivo neutralizing potency and a broad neutralization spectrum. The linear antibody binding site was mapped on the RV glycoprotein as antigenic site I by characterizing CR57 escape mutants. Secondly, we selected using phage display a complementing antibody (CR4098) that recognized a distinct, nonoverlapping epitope (antigenic site III), showed similar neutralizing potency and breadth as CR57, and neutralized CR57 escape mutants. Reciprocally, CR57 neutralized RV variants escaping CR4098. Analysis of glycoprotein sequences of natural RV isolates revealed that the majority of strains contain both intact epitopes, and the few remaining strains contain at least one of the two. In vitro exposure of RV to the combination of CR57 and CR4098 yielded no escape mutants. In conclusion, a novel combination of human MAbs was discovered suitable to replace RIG.
Anticoagulant activity of sulfonated polyrotaxanes as blood‐compatible materials (2002)

Polyrotaxanes, in which alpha-cyclodextrins (alpha-CDs) are threaded onto poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol) triblock copolymers (Pluronic) capped with benzyloxycarbonyl(Z)-L-phenylalanine (Z-L-Phe), were prepared, and sulfopropyl groups were introduced to hydroxyl groups of alpha-CDs in the polyrotaxanes. The supramolecular structure and the chemical composition of the polyrotaxanes after the sulfonation were confirmed by 1H-NMR, 13C-NMR, and elemental analysis. Anticoagulant activity of the polyrotaxanes and sulfonated polyrotaxanes was measured by activated partial thromboplastin time (APTT). It was found that the polyrotaxanes and the sulfonated polyrotaxanes showed greater anticoagulant activity than Pluronic itself, suggesting that both the supramolecular structure of the polyrotaxanes and the sulfonated groups contribute to the inhibition of intrinsic coagulation factors. Finally, our designed polyrotaxanes are suggested to be a promising candidate when fabricating blood-compatible medical devices by blending with or coating on clinically used polymers.
Some distance properties of latent root and vector methods used in multivariate analysis (1966)

This paper is concerned with the representation of a multivariate sample of size n as points P1, P2, …, Pn in a Euclidean space. The interpretation of the distance Δ(Pi, Pj) between the ith and jth members of the sample is discussed for some commonly used types of analysis, including both Q and R techniques. When all the distances between n points are known a method is derived which finds their co-ordinates referred to principal axes. A set of necessary and sufficient conditions for a solution to exist in real Euclidean sapce is found. Q and R techniques are defined as being dual to one another when they both lead to a set of n points with the same inter-point distances. Pairs of dual techniques are derived. In factor analysis the distances between points whose co-ordinrates are the estimated factor scores can be interpreted as D2 with a singular dispersion matrix.
Mapping of theNeisseria meningitidisNadA Cell-Binding Site: Relevance of Predicted α-Helices in the NH2-Terminal and Dimeric Coiled-Coil Regions (2010)

NadA is a trimeric autotransporter protein of Neisseria meningitidis belonging to the group of oligomeric coiled-coil adhesins. It is implicated in the colonization of the human upper respiratory tract by hypervirulent serogroup B N. meningitidis strains and is part of a multiantigen anti-serogroup B vaccine. Structure prediction indicates that NadA is made by a COOH-terminal membrane anchor (also necessary for autotranslocation to the bacterial surface), an intermediate elongated coiled-coil-rich stalk, and an NH(2)-terminal region involved in cell interaction. Electron microscopy analysis and structure prediction suggest that the apical region of NadA forms a compact and globular domain. Deletion studies proved that the NH(2)-terminal sequence (residues 24 to 87) is necessary for cell adhesion. In this study, to better define the NadA cell binding site, we exploited (i) a panel of NadA mutants lacking sequences along the coiled-coil stalk and (ii) several oligoclonal rabbit antibodies, and their relative Fab fragments, directed to linear epitopes distributed along the NadA ectodomain. We identified two critical regions for the NadA-cell receptor interaction with Chang cells: the NH(2) globular head domain and the NH(2) dimeric intrachain coiled-coil α-helices stemming from the stalk. This raises the importance of different modules within the predicted NadA structure. The identification of linear epitopes involved in receptor binding that are able to induce interfering antibodies reinforces the importance of NadA as a vaccine antigen.
Femtosecond real-time single-shot digitizer (2007)

We demonstrate a single-shot digitizer with a 10Tsample∕s sampling rate. This feat is accomplished with a photonic time stretch preprocessor that slows down the electrical waveform by an unprecedented factor of 250 before it is captured by a commercial electronic digitizer. To achieve such a large stretch factor, distributed Raman optical amplification is realized inside the dispersive element that performs the time stretch.
X-band two-stage high-efficiency switched-mode power amplifiers (2005)

This paper presents efficiency optimization of X-band two-stage microwave power amplifiers (PAs) in which the output stage is designed to operate in class-E mode. A hybrid PA which uses the same MESFET devices in both stages achieves 16 dB of saturated gain with an output power of 20 dBm and total power added efficiency (PAE) of 52% at 10 GHz. A broadband monolithic two-stage double heterojunction bipolar transistor PA, fabricated by Northrop Grumman Space Technology, with a class-AB first stage and class-E second stage achieves 24.6 dBm of output power with 24.6-dB gain and total PAE of 52% at 8 GHz. The design is performed starting from class-E theory and using load-pull measurements and/or nonlinear simulations.
Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model (2005)

The oral glucose minimal model (OMM) measures insulin sensitivity (S(I)) and the glucose rate of appearance (R(a)) of ingested glucose in the presence of physiological changes of insulin and glucose concentrations. However, S(I) of OMM measures the overall effect of insulin on glucose utilization and glucose production. In this study we show that, by adding a tracer to the oral dose, e.g., of a meal, and by using the labeled version of OMM, OMM* to interpret the data, one can measure the selective effect of insulin on glucose disposal, S(I)*. Eighty-eight individuals underwent both a triple-tracer meal with the tracer-to-tracee clamp technique, providing a model-independent reference of the R(a) of ingested glucose (R(a meal)(ref)) and an insulin-modified labeled intravenous glucose tolerance test (IVGTT*). We show that OMM* provides not only a reliable means of tracing the R(a) of ingested glucose (R(a meal)) but also accurately measures S(I)*. We do so by comparing OMM* R(a meal) with the model-independent R(a meal)(ref) provided by the tracer-to-tracee clamp technique, while OMM* S(I)* is compared with both S(I)(* ref), obtained by using as known input R(a meal)(ref), and with S(I)* measured during IVGTT*.
Hydrogen Supplied ICEs and Fuel Cells for Commercial Vehicles (2003)

Abstract In view of the limited availability of fossil fuels and the necessity to reduce the output of emissions of greenhouse gases in the long term, the transport sector needs efficient, environmentally compatible drive solutions. Hydrogen, as a clean and sustainable fuel, offers a high implementation potential and can be used both in internal combustion engines and in fuel cells. In urban deployment the fuel cell drive has specific advantages and is suitable for use in city buses. Integration of high‐power energy storage systems improves fuel consumption and can reduce the costs of the drive system. In May 2000 MAN presented its first fuel cell bus, which was successfully deployed in passenger transport in various cities. The next FC‐bus, using hybrid fuel cell propulsion, is planned under the framework of the Bavarian hydrogen project at Munich Airport and will be tested from spring 2004 on. The first deployment of pre‐series bus fleets with fuel cells using hydrogen as fuel can be expected from the end of this decade onwards.
Aligned Protein–Polymer Composite Fibers Enhance Nerve Regeneration: A Potential Tissue‐Engineering Platform (2007)

Sustained release of proteins from aligned polymeric fibers holds great potential in tissue-engineering applications. These protein-polymer composite fibers possess high surface-area-to-volume ratios for cell attachment, and can provide biochemical and topographic cues to enhance tissue regeneration. Aligned biodegradable polymeric fibers that encapsulate human glial cell-derived neurotrophic factor (GDNF, 0.13 wt%) were fabricated via electrospinning a copolymer of caprolactone and ethyl ethylene phosphate (PCLEEP) with GDNF. The protein was randomly dispersed throughout the polymer matrix in aggregate form, and released in a sustained manner for up to two months. The efficacy of these composite fibers was tested in a rat model for peripheral nerve-injury treatment. Rats were divided into four groups, receiving either empty PCLEEP tubes (control); tubes with plain PCLEEP electrospun fibers aligned longitudinally (EF-L) or circumferentially (EF-C); or tubes with aligned GDNF-PCLEEP fibers (EF-L-GDNF). After three months, bridging of a 15 mm critical defect gap by the regenerated nerve was observed in all the rats that received nerve conduits with electrospun fibers, as opposed to 50% in the control group. Electrophysiological recovery was seen in 20%, 33%, and 44% of the rats in the EF-C, EF-L, and EF-L-GDNF groups respectively, whilst none was observed in the controls. This study has demonstrated that, without further modification, plain electrospun fibers can help in peripheral nerve regeneration; however, the synergistic effect of an encapsulated growth factor facilitated a more significant recovery. This study also demonstrated the novel use of electrospinning to incorporate biochemical and topographical cues into a single implant for in vivo tissue-engineering applications.
Multi-Contrast Imaging and Digital Refocusing on a Mobile Microscope with a Domed LED Array (2015)

We demonstrate the design and application of an add-on device for improving the diagnostic and research capabilities of CellScope--a low-cost, smartphone-based point-of-care microscope. We replace the single LED illumination of the original CellScope with a programmable domed LED array. By leveraging recent advances in computational illumination, this new device enables simultaneous multi-contrast imaging with brightfield, darkfield, and phase imaging modes. Further, we scan through illumination angles to capture lightfield datasets, which can be used to recover 3D intensity and phase images without any hardware changes. This digital refocusing procedure can be used for either 3D imaging or software-only focus correction, reducing the need for precise mechanical focusing during field experiments. All acquisition and processing is performed on the mobile phone and controlled through a smartphone application, making the computational microscope compact and portable. Using multiple samples and different objective magnifications, we demonstrate that the performance of our device is comparable to that of a commercial microscope. This unique device platform extends the field imaging capabilities of CellScope, opening up new clinical and research possibilities.
Why cryptosystems fail (1993)

Designers of cryptographic systems are at a disadvantage to most other engineers, in that information on how their systems fail is hard to get: their major users have traditionally been government agencies, which are very secretive about their mistakes.
Oligolactate‐grafted dextran hydrogels: Detection of stereocomplex crosslinks by X‐ray diffraction (2002)

Abstract Physically crosslinked hydrogels are formed upon mixing equal amounts of aqueous solutions of dextran grafted with L ‐lactic acid oligomers and dextran grafted with D ‐lactic acid oligomers. In this paper, the dex‐lactate hydrogels are analyzed by X‐ray diffraction to provide evidence that hydrogel formation occurred through stereocomplex formation. First, the stereocomplex formation of monodisperse lactic acid oligomers was studied and comparison with published results of poly(lactic acid) was made. It was clearly demonstrated that stereocomplexes were formed between oligomers of opposite chirality. The data for these monodisperse lactic acid oligomers were used to interpret the results obtained with the dex‐lactate hydrogels. X‐ray diffraction measurements demonstrated that in the hydrogels stereocomplexes were formed between the lactic acid oligomers of opposite chirality. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 289–293, 2002
Improving compliance to colorectal cancer screening using blood and stool based tests in patients refusing screening colonoscopy in Germany (2014)

97% of subjects refusing colonoscopy accepted a non-invasive screening test of which 83% chose the Septin9 blood test. The observation that participation can be increased by offering non-invasive tests, and that a blood test is the preferred option should be validated in a prospective trial in the screening setting.
Acute formoterol administration has no ergogenic effect in nonasthmatic athletes (2015)

STEWART, I. B., J. M. LABRECHE, and D. C. McKENZIE. Acute formoterol administration has no ergogenic effect in nonasthmatic athletes. Med. Sci. Sports Exerc., Vol. 34, No. 2, pp. 213–217, 2002. Purpose To determine the effect of formoterol (formoterol fumarate dihydrate) on the aerobic and anaerobic capacities of highly trained athletes. Methods 10 male athletes (age = 26.2 ± 0.9, V̇O2max = 65.6 ± 2.4 mL·kg−1·min−1) with minimal bronchial reactivity to aerosols (i.e., negative methacholine challenge test) completed three identical exercise sessions differing only by the medication administered. Formoterol (F) a long-acting β2-agonist, presently not approved for international competition by the I.O.C. Medical committee, was compared with salbutamol (S), an accepted bronchodilator, and a placebo (P). Formoterol (12 μg), salbutamol (400 μg), or placebo was administered by a Turbuhaler, 10 min before exercise testing in a double-blind, randomized, three-way crossover design. Testing sessions included a Wingate anaerobic test followed 15 min later by an incremental cycle ergometer test to exhaustion. Results There were no significant differences between the groups in V̇O2max (F = 66.5 ± 2.7; S = 67.8 ± 2.5; P = 67.5 ± 2.1 mL·kg−1·min−1) or Wingate peak power (F = 885 ± 40; S = 877 ± 40; P = 885 ± 44 W) values. During the maximal aerobic test, no differences were observed in maximum minute ventilation, respiratory exchange ratio, heart rate, or work between the three experimental conditions. Also, there were no differences in the Wingate anaerobic test variables, total work, or fatigue index. Conclusion Formoterol, administered in one aerosolized therapeutic dose, does not have an ergogenic effect in elite athletes without asthma.
Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma (2014)

Bromodomain and extra terminal domain (BET) proteins are important epigenetic regulators facilitating the transcription of genes in chromatin areas linked to acetylated histones. JQ1, a BET protein inhibitor, has antiproliferative activity against many cancers, mainly through inhibition of c-MYC and upregulation of p21. In this research, we investigated the use of JQ1 for human osteosarcoma (OS) treatment. JQ1 significantly inhibited the proliferation and survival of OS cells inducing G1 cell cycle arrest, premature senescence, but little effect on apoptosis. Interestingly, c-MYC protein levels in JQ1-treated cells remained unchanged, whereas the upregulation of p21 protein was still observable. Although effective in vitro, JQ1 alone failed to reduce the size of the MNNG/HOS xenografts in immunocompromised mice. To overcome the resistance of OS cells to JQ1 treatment, we combined JQ1 with rapamycin, an mammalian target of rapamycin (mTOR) inhibitor. JQ1 and rapamycin synergistically inhibited the growth and survival of OS cells in vitro and in vivo. We also identified that RUNX2 is a direct target of bromodomain-containing protein 4 (BRD4) inhibition by JQ1 in OS cells. Chromatin immunoprecipitation (ChIP) showed that enrichment of BRD4 protein around RUNX2 transcription start sites diminished with JQ1 treatment in MNNG/HOS cells. Overexpression of RUNX2 protected JQ1-sensitive OS cells from the effect of JQ1, and siRNA-mediated inhibition of RUNX2 sensitized the same cells to JQ1. In conclusion, our findings suggest that JQ1, in combination with rapamycin, is an effective chemotherapeutic option for OS treatment. We also show that inhibition of RUNX2 expression by JQ1 partly explains the antiproliferative activity of JQ1 in OS cells.
Development of a multi-workstation laser processing facility (1983)

The considerations leading to the purchase of a 2kw CO2 laser and the expansion of the facility from a single work-station to the present system, are outlined. The development of the process for welding and cutting various metals, (including steels, nickel-based and titanium alloys) and the way it complements an existing, extensive manufacturing capability, is described. Plans for expansion of the system and further process development, (e.g. surface treatments; YAG Laser hole drilling) are outlined, as are the potential benefits from combining laser processing with other advanced metalworking processes such as superplastic forming.
Microbiological hydroxylation. Part XVIII. Introduction of 16α-, 9α-, and 3α-hydroxy-groups into dioxygenated 5α-androstanes by the fungus Diaporthe celastrina (1975)

Diaporthe celastrina, a fungus not previously reported as being active with steroids, hydroxylates a range of dioxygenated 5α-androstanes generally by attack on the α-face. The sites of hydroxylation and the efficiencies of the processes depend on the positions and oxidation levels of the androstanes' substituents. 5α-Androstane-3,7-dione is converted into 3β,16α-dihydroxy-5α-androstan-7-one (45% yield); 3β-hydroxy-5α-androstan-17-one is hydroxylated in the 9α-position (55%), and 5α-androstane-7,17-dione gives the 3α-hydroxy-derivative (52%).
An advanced radar technique for electron density measurements on large Tokamaks (1993)

A new way to measure the electron density profile bymicrowave reflectometry is studied. The idea is to use apulse compression millimeter waves radar. Thetechnique is discussed and laboratory measurements andsimulations are presented.