gebhart/patrepeval huggingface dataset:
Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma (2015)

Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem as serial re-biopsy of primary tumours is often not a clinical option. MGMT (O(6)-methylguanine DNA methyltransferase) and APNG (alkylpurine-DNA-N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA damages and their levels in tissue are inversely related to treatment efficacy. Yet, serial clinical analysis remains difficult, and, when done, primarily relies on promoter methylation studies of tumour biopsy material at the time of initial surgery. Here we present a microfluidic chip to analyse mRNA levels of MGMT and APNG in enriched tumour exosomes obtained from blood. We show that exosomal mRNA levels of these enzymes correlate well with levels found in parental cells and that levels change considerably during treatment of seven patients. We propose that if validated on a larger cohort of patients, the method may be used to predict drug response in GBM patients.
Resolution limits for imaging through multi-mode fiber (2013)

We experimentally demonstrate endoscopic imaging through a multi-mode fiber (MMF) in which the number of resolvable image features approaches four times the number of spatial modes per polarization propagating in the fiber. In our method, a sequence of random field patterns is input to the fiber, generating a sequence of random intensity patterns at the output, which are used to sample an object. Reflected power values are returned through the fiber and linear optimization is used to reconstruct an image. The factor-of-four resolution enhancement is due to mixing of modes by the squaring inherent in field-to-intensity conversion. The incoherent point-spread function (PSF) at the center of the fiber output plane is an Airy disk equivalent to the coherent PSF of a conventional diffraction-limited imaging system having a numerical aperture twice that of the fiber. All previous methods for imaging through MMF can only resolve a number of features equal to the number of modes. Most of these methods use localized intensity patterns for sampling the object and use local image reconstruction.
AN INTERSEX PIG WITH XX/XY LEUCOCYTE MOSAICISM (1966)

There have been several recent reports on the genetic charactristics of pigs with varying degrees of intersexuality (Johnston e t al., 1958; Adaltino e t al., 1962; Hcnricson and Baclatrijm, 1963; Gernelte, 1964a; Hard and Eisen, 1965; Renzoni, 1965; and Vogt, 1966). The reported animals were striltingly similar in that they all possessed only cells with a female complement. Indeed, it has almost become accepted that porcine sex variants, whether pseudohermaphrodites or true intersexes, are always genetically female. The animal described in this report indicates that intersex pigs in some cases are genetically sex mosaics.
Discrete elements for 3D microfluidics (2014)

Microfluidic systems are rapidly becoming commonplace tools for high-precision materials synthesis, biochemical sample preparation, and biophysical analysis. Typically, microfluidic systems are constructed in monolithic form by means of microfabrication and, increasingly, by additive techniques. These methods restrict the design and assembly of truly complex systems by placing unnecessary emphasis on complete functional integration of operational elements in a planar environment. Here, we present a solution based on discrete elements that liberates designers to build large-scale microfluidic systems in three dimensions that are modular, diverse, and predictable by simple network analysis techniques. We develop a sample library of standardized components and connectors manufactured using stereolithography. We predict and validate the flow characteristics of these individual components to design and construct a tunable concentration gradient generator with a scalable number of parallel outputs. We show that these systems are rapidly reconfigurable by constructing three variations of a device for generating monodisperse microdroplets in two distinct size regimes and in a high-throughput mode by simple replacement of emulsifier subcircuits. Finally, we demonstrate the capability for active process monitoring by constructing an optical sensing element for detecting water droplets in a fluorocarbon stream and quantifying their size and frequency. By moving away from large-scale integration toward standardized discrete elements, we demonstrate the potential to reduce the practice of designing and assembling complex 3D microfluidic circuits to a methodology comparable to that found in the electronics industry.
Bioadhesive Drug Delivery System Using Glyceryl Monooleate for the Intravesical Administration of Paclitaxel (2005)

We conclude that GMO has a significantly increased bioadhesiveness to bladder mucosa. Therefore, intravesical administration of GMO/paclitaxel/water provides a significant advantage for drugs targeting the bladder tissue, and paclitaxel represents a viable option for intravesical bladder cancer therapy.
Characterization of lipoprotein particles isolated by immunoaffinity chromatography. Particles containing A-I and A-II and particles containing A-I but no A-II. (1984)

Two populations of A-I-containing lipoprotein particles: A-I-containing lipoprotein with A-II (Lp (A-I with A-II], and A-I-containing lipoprotein without A-II (Lp (A-I without A-II] have been isolated from plasma of 10 normolipidemic subjects by immunoaffinity chromatography and characterized. Both types of particles possess alpha-electrophoretic mobility and hydrated density in the range of plasma high-density lipoproteins (HDL). Lp (A-I without A-II) and Lp (A-I with A-II) are heterogeneous in size. Lp (A-I without A-II) comprised two distinct particle sizes with mean apparent molecular weight and Stokes diameter of 3.01 X 10(5), and 10.8 nm for Lp (A-I without A-II)1, and 1.64 X 10(5), and 8.5 nm for Lp (A-I without A-II)2. Lp (A-I with A-II) usually contained particles of at least three distinct molecular sizes with mean apparent molecular weight and Stokes diameter of 2.28 X 10(5) and 9.6 nm for Lp (A-I with A-II)1, 1.80 X 10(5) and 8.9 nm for Lp (A-I with A-II)2, and 1.25 X 10(5) and 8.0 nm for Lp (A-I with A-II)3. Apoproteins C, D, and E, and lecithin:cholesterol acyltransferase (LCAT) were detected in both Lp (A-I without A-II) and Lp (A-I with A-II) with most of the apoprotein D, and E, and LCAT (EC 2.3.1.43) in Lp (A-I with A-II) particles. Lp (A-I without A-II) had a slightly higher lipid/protein ratio than Lp (A-I with A-II). Lp (A-I with A-II) had an A-I/A-II molar ratio of approximately 2:1. The percentage of plasma A-I associated with Lp (A-I without A-II) was highly correlated with the A-I/A-II ratio of plasma (r = 0.96, n = 10). The variation in A-I/A-II ratio of HDL density subfractions therefore reflects different proportions of two discrete types of particles: particles containing A-I and A-II in a nearly constant ratio and particles containing A-II but no A-II. Each type of particle is heterogeneous in size and in apoprotein composition.
Induction of glucose regulated proteins during growth of a murine tumor (1993)

Chronic anoxia, glucose starvation, low pH, and numerous other conditions induce the glucose-regulated system of stress proteins (GRPs), whose principal members are observed at 78, 94, and 170 kDa. These stresses may be expected to occur during growth in untreated tumors. To examine the possibility that GRPs are correspondingly induced, we have examined the protein profiles of small (< 0.1 g), intermediate (0.2-0.8 g), and large (> 1.8 g) radiation-induced fibrosarcoma (RIF) tumors grown on C3H mice. One and two-dimensional gel electrophoresis indicate that the principal GRPs at 78 and 94 are coordinately and substantially increased in large tumor masses, relative to the small, and may be partially increased in the intermediate tumors. Necrotic material removed from large tumors exhibited an identical pattern of GRP induction with no visible indication of protein degradation and also contained a significant fraction of viable cells. Western blot analysis using rabbit antisera raised against the 78 and 170 kDa GRPs also demonstrated the enhanced accumulation of these proteins in the large tumors. The antibody against the 170 kDa GRP was also capable of detecting the induction of this stress protein in large tumors by indirect immunofluorescence analysis. Northern blot studies using a probe for the GRP 78 gene also showed an increase in GRP 78 message in large tumors as well as in RIF cells exposed to anoxic stress in vitro. Two-dimensional gel electrophoresis indicated that the major heat shock proteins at 70 and 90 kDa were not increased in the larger tumors, and the amount of the 90 kDa species was reduced. Finally, the quantity of vimentin and its degradation products is significantly diminished in large tumors and in anoxic cells. This study demonstrates that RIF tumor cells undergo a glucose regulated stress response in situ during tumor growth.
Effects of the conditions for electron beam irradiation on the amounts of volatiles from irradiated polyethylene film. (1984)

The effects of conditions for electron beam irradiation on the amounts of volatiles from irradiated polyethylene film were studied. The concentration of oxygen up to 5%in the atmosphere affected the amounts of carbonyl compounds, and their amounts decreased remarkably with a decrease in the concentration of oxygen. A low irradiation temperature of -75°C, a radiation energy of 1.5 MeVor lower, and a higher beamcurrent were effective in reducing the amounts of volatiles formed by irradiation. The effect of conveyor speed was not so significant. It has also been found that electron beam irradiation is better in restraining the formation of volatiles than γ-irradiation.
A novel and efficient solution to block-based joint-detection using approximate Cholesky factorization (2002)

Despite the fact that the zero-forcing block-linear equalizer (ZF-BLE) represents an entry-level solution to the joint-detection problem as applied to the TD-CDMA air-interface proposal for UMTS, it is nevertheless accompanied by a prohibitive computational complexity when supporting long data sequences, multiple users and channels with long impulse responses. A primary contributor to this computational complexity is the need to perform a Cholesky factorization of a sparse yet large correlation matrix. This paper presents a novel technique which exploits the pseudo block-Toeplitz nature of the Cholesky factor to derive an approximate triangular factorization, thereby allowing significant reductions in computational complexity and finite-precision effects at the expense of little or no degradation in performance. The technique is equally applicable to other block-based linear or decision-feedback joint-detection schemes whose operation relies on the Cholesky factorization.
Receptor-mediated endocytosis in Xenopus oocytes. II. Evidence for two novel mechanisms of hormonal regulation. (1987)

Xenopus oocytes exhibit enhanced rates of vitellogenin (VTG) endocytosis following exposure to insulin in vitro and human chorionic gonadotropin in vivo. We investigated this phenomenon using kinetic and steady state analyses and found that the stimulation of VTG uptake was not due to an increase in surface VTG receptors. Instead, both hormones acted by stimulating the specific internalization rate (ke) of the VTG receptor, although by apparently different mechanisms. The stimulation of ke by insulin was most obvious at low levels of receptor occupancy. Insulin also increased the affinity of the VTG receptor for its ligand. Both hormones increased the rate of fluid phase endocytosis, but the magnitude of stimulation was not sufficient to account for the observed increase in VTG uptake. The steady state binding of VTG was biphasic with respect to increasing ligand concentration, primarily due to a nonlinear receptor internalization rate as a function of occupancy. The nonlinear VTG binding was abolished by incubating the oocytes at 0 degree C. Our data are consistent with a model in which there is a cell surface regulatory component that facilitates the internalization of the occupied VTG receptor. Although both human chorionic gonadotropin and insulin stimulate VTG uptake by increasing the net rate of endocytosis, insulin also increases the association of the occupied VTG receptor with this regulatory component.
Muscle in Lafora Disease (1974)

Ultrastructural studies of muscle from a patient with Lafora disease showed sheets of glycogen particles and fine granular-filamentous material between myofibrils. These structures were frequently intermingled and stained intensely with silver proteinate, a specific stain for polysaccharides. Methods for isolation of glycogen yielded excessive hexose-releasing material. In chromatographic analysis of a hydrolysate of this material, glucose was the only component sugar. Compared with action on normal muscle glycogen, phosphorylase was ineffective, β-amylase 50% less effective, but α-amylase normally effective in degrading the Lafora polyglucosan. Incubation of muscle homogenate or isolated polyglucosan with a mixture of glucosidases capable of completely degrading normal glycogen (Diazyme) resulted in only 30% digestion of the Lafora polyglucosan. The metabolic error causing the accumulation of anomalous polysaccharide in this generalized storage disease remainsobscure.
Inhibitors of slit protein interactions with the heparan sulphate proteoglycan glypican‐1: Potential agents for the treatment of spinal cord injury (2009)

1. The heparan sulphate proteoglycan glypican-1 is a major high-affinity ligand of the Slit proteins. 2. Messenger RNA for both Slit-2 and glypican-1 is strongly upregulated and coexpressed in the reactive astrocytes of injured adult brain, suggesting a possible function of Slit proteins and glypican-1 in the adult central nervous system as significant components of the inhibitory environment that prevents axonal regeneration after injury. 3. Based on the hypothesis that adverse effects on axonal regeneration may be due to a glypican-Slit complex or the retention of glypican-binding C-terminal proteolytic processing fragments of Slit at the injury site, we used ELISA to examine a number of small molecules and low molecular weight heparin analogues for their ability to inhibit glypican-Slit interactions. 4. Our studies have led to the identification of several potent inhibitors with a favourable therapeutic profile that can now be tested in a spinal cord injury model. Among the most promising of these are a low molecular weight heparin produced by periodate oxidation and having no significant anticoagulant activity, the chemically sulphonated yeast-derived phosphomannan PI-88 and a number of randomly derivatized water-soluble sulphated dextrans.
5-ht6 Receptors as Emerging Targets for Drug Discovery (2000)

5-ht6 receptors are the latest serotonin receptors to be identified by molecular cloning. Their high affinity for a wide range of drugs used in psychiatry, coupled with their intriguing distribution in the brain, has stimulated significant interest. Antisense oligonucleotides, antipeptide antibodies, selective radioligands, knockout mice, and selective antagonists of the 5-ht6 receptor have recently become available. Surprisingly, 5-ht6 receptors appear to regulate cholinergic neurotransmission in the brain, rather than the expected interaction as modulators of dopaminergic transmission. This interaction predicts a possible role for 5-ht6 receptor antagonists in the treatment of learning and memory disorders. Furthermore, polymorphisms in the sequence of the 5-ht6 receptor gene may provide a genetic tool to further our understanding of the differential responses of patients to antipsychotic medications.
The role of nuclear factor-kappaB in the development of autoimmune diseases: a link between genes and environment. (2008)

Although autoimmune diseases are relatively common, mechanisms that lead to their development remain largely unknown. Nuclear factor-kappaB (NF-kappaB), as a key transcription factor involved in the regulation of immune responses and apoptosis, appears to be a good candidate for studies on the pathogenesis of autoimmunity. This review presents how perturbations of the NF-kappaB signaling pathway may contribute to self-tolerance failure, initiation of autoimmune inflammatory response as well as its persistent maintenance and therefore to the development of common autoimmune diseases including rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, thyroid autoimmune diseases, systemic lupus erythematosus as well as inflammatory bowel diseases and psoriasis. A special emphasis is put on the genetic variations in the NF-kappaB related genes and their possible association with susceptibility to autoimmune diseases, as well as on the therapeutic potential of the NF-kappaB targeted strategies in the treatment of autoimmunity.
Assemblies of Aligned Magnetotactic Bacteria and Extracted Magnetosomes: What Is the Main Factor Responsible for the Magnetic Anisotropy? (2009)

The origin of the magnetic anisotropy is explained in an assembly of aligned magnetic nanoparticles. For that, nanoparticles synthesized biologically by Magnetospirillum magneticum AMB-1 magnetotactic bacteria are used. For the first time, it is possible to differentiate between the two contributions arising from the alignment of the magnetosome easy axes and the strength of the magnetosome dipolar interactions. The magnetic anisotropy is shown to arise mainly from the dipolar interactions between the magnetosomes.
Acid-Labile Traceless Click Linker for Protein Transduction (2012)

Intracellular delivery of active proteins presents an interesting approach in research and therapy. We created a protein transduction shuttle based on a new traceless click linker that combines the advantages of click reactions with implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic anhydride (AzMMMan) linker was found compatible with different click chemistries, demonstrated in bioreversible protein modification with dyes, polyethylene glycol, or a transduction carrier. Linkages were stable at physiological pH but reversible at the mild acidic pH of endosomes or lysosomes. We show that pH-reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane amino)amide carrier generates an effective shuttle for protein delivery. The cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences efficient cellular uptake and endosomal escape into the cytosol, followed by import into the nucleus. In contrast, irreversible linkage to the same shuttle hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the cytosol. Successful intracellular delivery of bioactive ß-galactosidase as a model enzyme was also demonstrated using the pH-controlled shuttle system.
Carotenoids : chemistry and biology (1989)

In the mid-1960's, scientists working on carotenoids throughout the World agreed to have periodic meetings for the purpose of discussing and disseminating scientific research results concerning all aspects of carotenoids. The meetings were also organized to act as teaching forums for students, and the major scientific results from each meeting were to result in a publication. Each meeting was planned to be International in scope, being held in different locations in the World, and organized by local, recognized carotenoid scientists. The first of the Carotenoid meetings was held in Trondheim, Norway in 1966. Meetings then followed in Las Cuces, New Mexico (1969); Cluj, Roumania (1972); Berne, Switzerland (1975); Madison, Wisconsin (1978); Liverpool; England (1981); and Munich, Federal Republic of Germany (1984). In all of these meetings, the original purposes which stimulated the first meeting were accomplished: scientific discussion, student education and resulting scientific publication.The meetings and the i formation resulting from them have led to significant advances in carotenoid biochemistry, biology, and chemisty. This publication represents the contributions from a distinguished list of participants. We look forward to the future meetings in this series.
Accelerating best response calculation in large extensive games (2011)

One fundamental evaluation criteria of an AI technique is its performance in the worst-case. For static strategies in extensive games, this can be computed using a best response computation. Conventionally, this requires a full game tree traversal. For very large games, such as poker, that traversal is infeasible to perform on modern hardware. In this paper, we detail a general technique for best response computations that can often avoid a full game tree traversal. Additionally, our method is specifically well-suited for parallel environments. We apply this approach to computing the worst-case performance of a number of strategies in heads-up limit Texas hold'em, which, prior to this work, was not possible. We explore these results thoroughly as they provide insight into the effects of abstraction on worst-case performance in large imperfect information games. This is a topic that has received much attention, but could not previously be examined outside of toy domains.
Intravenous Ferric Carboxymaltose Accelerates Erythropoietic Recovery From Experimental Malarial Anemia (2012)

Iron restriction has been proposed as a cause of erythropoietic suppression in malarial anemia; however, the role of iron in malaria remains controversial, because it may increase parasitemia. To investigate the role of iron-restricted erythropoiesis, A/J mice were infected with Plasmodium chabaudi AS, treated with intravenous ferric carboxymaltose at different times, and compared with untreated controls. Iron treatment significantly increased weight and hemoglobin nadirs and provided enhanced reticulocytosis and faster recovery, compared with controls. Our findings challenge the restrictive use of iron therapy in malaria and show the need for trials of intravenous ferric carboxymaltose as an adjunctive treatment for severe malarial anemia.
Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease (1992)

This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release-controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases.