gebhart/patrepeval huggingface dataset:
Identifying Novel Targetable Genes and Pathways in Cancer by Integrating Diverse Omics Data. (2013)

Omics technologies for high-throughput profiling of human genome, transcriptome and proteome are revolutionizing cancer research and driving a paradigm shift in clinical care, from “one size” fits all treatments to molecularly informed therapies. The success of this new precision medicine paradigm will depend on our ability to combine diverse omics-based measurements to distill clinically relevant information that can be acted upon. This thesis developed bioinformatics approaches to integrate multi-omics datasets and applied these approaches in three distinct studies that identified novel actionable genes and pathways in cancer. In the first study, we aim at finding alternative targetable proteins in non-small cell lung cancers (NSCLC) with activating mutations in KRAS, a well-know but undruggable oncogene, by profiling their transcriptome, proteome and phosphoproteome. By reconstructing targetable networks associated with KRAS dependency, we nominate lymphocyte-specific protein tyrosine kinase (LCK) as a critical gene for cell proliferation in these samples, suggesting LCK as a novel druggable protein in KRAS-dependent NSCLC. In the second study, we aim at identifying oncogenic gene fusions in NSCLC patients of unknown driver gene. By characterizing the highly heterogeneous fusion’s landscape in NSCLC, we show that gene fusions incidence is an independent prognostic factor for poor outcome and discover novel Neurorregulin 1 (NRG1) fusions present exclusively in patients of unknown driver; resembling previously reported kinase fusions. This warrants further studies of the therapeutic opportunities for patients with NRG1 rearrangements. Finally in the third study, we aim at characterizing cancer-related genes that overlap and could be regulated by natural antisense transcripts. By determining the extent of antisense gene expression across human cancers and comparing with well-documented sense-antisense pairs, our results raise the possibility that antisense transcripts could modulate the expression of well-known tumor suppressors and oncogenes. This study provides a resource, oncoNATdb, a catalogue of cancer related genes with significant antisense transcription, which will enable researchers to investigate the mechanisms of sense-antisense regulation and their role in cancer. We anticipate that the computational methods developed and the results found in this thesis would assist others with similar tasks and inspire further studies of the therapeutic opportunities provided by these novel targets.
Polymerization of coordinated monomers. XIX. Kinetic study of the alternating copolymerization of methyl methacrylate with styrene by boron trichloride (1982)

Abstract Alternating copolymerizations of methyl methacrylate with styrene in the presence of boron trichloride at 0°C in 1,2‐dichloroethane were carried out by using benzoyl peroxide as an initiator. Conversion increased proportionally with polymerization time, whereas the degree of polymerization was constant irrespective of time. The rate depended linearly on the square root of the concentration of benzoyl peroxide. The equilibrium constants for the formation of the ternary molecular complex composed of methyl methacrylate, styrene, and boron trichloride in 1,2‐dichloroethane at −20, −10, and +4°C were determined by 1 H‐NMR spectroscopy. The concentrations of the ternary molecular complex in the polymerization mixtures were evaluated from the equilibrium constant of the formation. The rate of the alternating copolymerization was proportional to the first order of the concentration of the ternary molecular complex. The distribution of methyl methacrylate‐centered triads in the alternating copolymer was different from that of styrene‐centered triads. These results can be explained by a mechanism involving the homopolymerization of a ternary molecular complex.
Cleavage of nonphenolic β‐1 diarylpropane lignin model dimers by manganese peroxidase from <i>Phanerochaete chrysosporium</i> (2003)

Purified manganese peroxidase (MnP) from Phanerochaete chrysosporium oxidizes nonphenolic beta-1 diarylpropane lignin model compounds in the presence of Tween 80, and in three- to fourfold lower yield in its absence. In the presence of Tween 80, 1-(3',4'-diethoxyphenyl)-1-hydroxy-2-(4'-methoxyphenyl)propane (I) was oxidized to 3,4-diethoxybenzaldehyde (II), 4-methoxyacetophenone (III) and 1-(3',4'-diethoxyphenyl)-1-oxo-2-(4'-methoxyphenyl)propane (IV), while only 3,4-diethoxybenzaldehyde (II) and 4-methoxyacetophenone (III) were detected when the reaction was conducted in the absence of Tween 80. In contrast to the oxidation of this substrate by lignin peroxidase (LiP), oxidation of substrates by MnP did not proceed under anaerobic conditions. When the dimer (I) was deuterated at the alpha position and subsequently oxidized by MnP in the presence of Tween 80, yields of 3,4-diethoxybenzaldehyde, 4-methoxyacetophenone remained constant, while the yield of the alpha-keto dimeric product (IV) decreased by approximately sixfold, suggesting the involvement of a hydrogen abstraction mechanism. MnP also oxidized the alpha-keto dimeric product (IV) to yield 3,4-diethoxybenzoic acid (V) and 4-methoxyacetophenone (III), in the presence and, in lower yield, in the absence of Tween 80. When the reaction was performed in the presence of 18O2, both products, 3,4-diethoxybenzoic acid and 4-methoxyacetophenone, contained one atom of 18O. Finally, MnP oxidized the substrate 1-(3',5'-dimethoxyphenyl)-1-hydroxy-2-(4'-methoxyphenyl)propane (IX) to yield 3,5-dimethoxybenzaldehyde (XI), 4-methoxyacetophenone (III) and 1-(3',5'-dimethoxyphenyl)-1-oxo-2-(4'-methoxyphenyl)propane (X). In sharp contrast, LiP was not able to oxidize IX. Based on these results, we propose a mechanism for the MnP-catalyzed oxidation of these dimers, involving hydrogen abstraction at a benzylic carbon, rather than electron abstraction from an aromatic ring.
<b><i>In vitro</i> characterization of constitutive CysB proteins from <i>Salmonella typhimurium</i></b> (1996)

Expression of the cysteine regulon in Salmonella typhimurium and Escherichia coli is controlled by the LysR-type transcriptional activator CysB and by the inducer N-acetyl-L-serine. Sulphide and thiosulphate are anti-inducers. Two highly purified constitutive CysB proteins, CysB(T149M) and CysB(T149P), were found to bind to the cysJIH, cysK and cysP promoters, to activate transcription from the cysJIH and cysK promoters in the absence of N-acetyl-L-serine, and to be insensitive to the effects of anti-inducers. At 10 mM MgCl2, the in vitro transcription activity of CysB(T149M) was maximal without N-acetyl-L-serine, but that of CysB(T149P) was increased by inducer. At 2 mM MgCl2, both proteins were fully active without inducer. A third mutant protein, CysB(W166R), was totally inactive at 10 mM MgCl2, but gave constitutive expression of the cysK and cysJIH promoters at 2 mM MgCl2. Surprisingly, wild-type CysB was also constitutive for the cysK promoter at 2 mM mgCl2 but not at 10 mM MgCl2; it required inducer for cysJIH promoter activation at both concentrations. Mutagenic studies indicated that this difference between promoters is due to the distance between activation site half-sites, which are separated by 1 bp in the cysJIH promoter and by 2 bp in the cysK promoter. We speculate that inducer acts to decrease the distance between the binding domains of two CysB subunits that interact with an activation site. In vitro activities of wild-type and mutant CysB proteins correlated much better with in vivo behaviour at 2 mM than at 10 mM MgCl2, suggesting that the former is the more physiological concentration.
Cu/Sn microbumps interconnect for 3D TSV chip stacking (2010)

The electronics industry is increasingly looking to 3D integration in order to address the ever continuing product needs of miniaturization and performance increase for future generation of ICs. Most of these integration schemes require multiple die stacking on top of each other. In this work, transient liquid phase (TLP) bonding technique using Cu-Sn intermetallic is used for die stacking. Fast die to wafer pick and place operation followed by collective bonding process is described here for bonding application. Low temperature stacking is also explored using solid metal bonding (SMB) process and the effect of various cleaning agents on the bonding interface is discussed. Finally, in this paper we report on die stacking using microbumps with dies containing through silicon visa (TSV).
Japanese dependency structure analysis based on support vector machines (2000)

This paper presents a method of Japanese dependency structure analysis based on Sup-port Vector Machines (SVMs). Conventional parsing techniques based on Machine Learning framework, such as Decision Trees and Maximum Entropy Models, have difficulty in selecting useful features as well as finding appropriate combination of selected features. On the other hand, it is well-known that SVMs achieve high generalization performance even with input data of very high dimensional feature space. Furthermore, by introducing the Kernel principle, SVMs can carry out the training in high-dimensional spaces with a smaller computational cost independent of their dimensionality. We apply SVMs to Japanese dependency structure identification problem. Experimental results on Kyoto University corpus show that our system achieves the accuracy of 89.09% even with small training data (7958 sentences).
Oversegment an image to get the candidate detection windows (2009)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Effects of LiF Addition in Lithium Ion Conductor La<sub>0.56</sub>Li<sub>0.33</sub>TiO<sub>3</sub> (2010)

The compositions La0.56Li0.33TiO2.95F0.05•xLiF (x=0-025) were prepared by addition of LiF to the disordered form of the well-known Li ion conductor La0.56Li0.33TiO3. Although the total conductivities improved, there was no change in the bulk conductivity with LiF addition. No reflections due to LiF were observed in their XRD patterns, and the profiles and the chemical shifts of their 19F MAS-NMR resonances were almost the same as those of LiF. The results indicate that no substitution of F takes place, and that the added LiF acts simply as a sintering assistant agent.
Solubility and stability enhancement of atorvastatin by cyclodextrin complexation. (2010)

The objective of the study was to increase the solubility, stability, and dissolution rate of atorvastatin calcium (ATN Ca), a poorly water-soluble 3-hydroxy 3-methyl glutaryl CoA (HMG-CoA) reductase inhibitor through inclusion complexation with beta-cyclodextrin (beta-CD). The phase solubility profile indicated that the solubility of ATN Ca was significantly increased in the presence of beta-CD and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Solid complexes prepared by physical mixing, kneading, co-evaporation, and freeze-drying methods were characterized using differential scanning calorimetry, fourier transform infrared spectroscopy, and powder X-ray diffractometry. In vitro studies showed that the solubility and dissolution rate of ATN Ca were significantly improved by complexation with beta-CD with respect to the drug alone. In contrast, freeze-dried product showed higher solubility and dissolution rates than the other complexes. ATN Ca unit dosage form was developed and evaluated for physico-chemical properties, stability, and dissolution rate. The stability of tablets was studied and no significant changes were detected in the dissolution profile of tablets after 1 month.
Graphene p–n Vertical Tunneling Diodes (2013)

Formation and characterization of graphene p-n junctions are of particular interest because the p-n junctions are used in a wide variety of electronic/photonic systems as building blocks. Graphene p-n junctions have been previously formed by using several techniques, but most of the studies are based on lateral-type p-n junctions, showing no rectification behaviors. Here, we report a new type of graphene p-n junction. We first fabricate and characterize vertical-type graphene p-n junctions with two terminals. One of the most important characteristics of the vertical junctions is the asymmetric rectifying behavior showing an on/off ratio of ~10(3) under bias voltages below ±10 V without gating at higher n doping concentrations, which may be useful for practical device applications. In contrast, at lower n doping concentrations, the p-n junctions are ohmic, consistent with the Klein-tunneling effect. The observed rectification results possibly from the formation of strongly corrugated insulating or semiconducting interlayers between the metallic p- and n-graphene sheets at higher n doping concentrations, which is actually a structure like a metal-insulator-metal or metal-semiconductor-metal tunneling diode. The properties of the diodes are almost invariant even 6 months after fabrication.
Acidified nitrite enhances hydrogen peroxide disinfection of Acanthamoeba, bacteria and fungi (2010)

The findings of this study demonstrate that acidified NaNO2 can significantly enhance the antimicrobial activity of H2O2 probably through the generation of peroxynitrite. The addition of acidified nitrite to 3% (v/v) H2O2 solution may represent an improved one-step method for the disinfection of contact lenses, especially against highly resistant cysts of Acanthamoeba spp.
Vascular distensibility and vascular surgery. (1985)

The elastic property of an arterial wall decreases considerably with aging and/or with a variety of pathological conditions. The resulting decrease in vascular compliance has a profound physiological effect on arterial perfusion. The objectives of this study were to assess a quantitative measure of peripheral vascular distensibility (D), to apply it in some clinical conditions, and to establish a potential means of predicting success in vascular surgery for limb salvage. A technique described earlier by us for the determination of D based on an accurate measurement of volume change (delta V) with pressure change (delta P) was further analyzed and then tested in four groups: the first two were non-surgical, 18 normal subjects, and 23 hypertensive men paired with 22 normotensive men; the last two were surgical, patients undergoing aortofemoral bypass (AFB) operations for limb salvage (salvaged vs unsalvaged); and patients who underwent below-knee amputations (BKA) for severe arterial insufficiency (healed vs unhealed). The results indicate that D can be used as a reliable assessment of the pathophysiological status of the arterial system in the lower extremity; furthermore, D can be used as a predictor of success in at least two types of vascular procedures: AFB with profundoplasty for limb salvage and BKA for severe arterial insufficiency.
Thermo-optic dispersion properties of aluminum nitride with an optical waveguide technique (2002)

An aluminum nitride thin film on sapphire substrate was prepared by metal-organic chemical-vapor deposition for optical waveguide study. In order to investigate thermo-optic dispersion properties of aluminum nitride waveguide, a new experimental arrangement is designed. The thermo-optic properties of thin film are obtained using a prism coupled waveguide devices, which has auto-temperature controlling system. The temperature range is 30 ° C — 85° C with the control accuracy of ± 1 ° C. The experiment was carried out by using different light source with wavelength of 441.6 nm, 514.5 nm, and 632.8nm. A set of curve of thermo-optic dispersion of aluminum nitride film is given.
Cellular and cytokine kinetics after epicutaneous allergen challenge (atopy patch testing) with house dust mites in high‐IgE beagles (2006)

The cellular and cytokine dynamics of reactions triggered by atopy patch testing with house dust mites were studied in six high-IgE beagles. Sites were scored and biopsied at 6, 24, 48, and 96 h, and samples were processed for histopathology, immunohistochemistry, and polymerase chain reaction (PCR). All dogs developed positive reactions at some point in time. Mean clinical scores were significantly higher than baseline at 24, 48, and 96 h. Clinically, one of six dogs had a positive reaction at 6 h; two of six reacted at 24 and 48 h, and five of six at 96 h. Histologically, superficial perivascular mononuclear and granulocytic dermatitis developed (5/6) after 6 h, and progressed in severity at 24 h (6/6). Additionally, at 48 h epidermal spongiosis, hyperplasia and pustules developed (5/6), and were marked at 96 h (6/6). At and beyond 6 h, progressive CD1c-positive epidermal Langerhans cell hyperplasia with cluster formation and dermal dendritic cell infiltration was noted. Cutaneous infiltration of CD3-positive T lymphocytes with epidermal clusters developed over time. mRNA expression for the cytokines gamma-interferon (gamma-IFN), interleukin-6 (IL-6), IL-12p35, IL-13, IL-18, and thymus and activation regulated chemokine (TARC) exhibited significant increases during the challenge compared to baseline, but there was no appreciable alteration in expression for tumour necrosis factor-alpha (TNF-alpha), IL-12p40, IL-10, regulated on activation normal T-cell expressed and secreted (RANTES), IL-5, IL-2, IL-4, and IL-8. No correlation was detected between clinical scores and cytokines. It is concluded that IL-6 plays a role in early reactions followed by an increase of TARC and IL-13, while IL-18 progressively increases in later reactions.
Four‐center type photopolymerization in the solid state. III. Polymerization of phenylene diacrylic acid and its derivatives (1969)

Abstract The solid‐state photopolymerization of phenylene diacrylic acid (PDA) and its derivatives was studied as an application of solid‐state photodimerization of cinnamic acid to photopolymerization of corresponding bifunctional molecule which has two cinnamic units in a single molecule. p ‐ and m ‐PDA, and their esters and amides were prepared and investigated with respect to their photopolymerizability. Many of them have been found to polymerize into linear high polymers with the cyclobutane rings in the main chain on irradiation by ultraviolet or visible light. The polymerization process, the structure of the polymers, and their general properties were investigated in several ways. All the polymers are very similar to poly‐2,5‐distyrylpyrazine and poly‐1,4‐bis(β‐pyridyl‐2‐vinyl) benzene with respect to their polymerization behavior, polymer structure, and some polymer properties: these polymers are soluble in a limited number of solvents, they have a high melting point and an extremely high crystallinity. On the basis of chemical behavior of poly‐PDA and its phenyl ester the possible steric configurations of these polymers are discussed. It is demonstrated for the PDA series that solid‐state dimerization can be generally extended to solid‐state photopolymerization of the compound having two dimerizable units in a single molecule, although the crystal structure renders polymerization impossible in certain cases.
Softmax Regression Design for Stochastic Computing Based Deep Convolutional Neural Networks (2017)

Recently, Deep Convolutional Neural Networks (DCNNs) have made tremendous advances, achieving close to or even better accuracy than human-level perception in various tasks. Stochastic Computing (SC), as an alternate to the conventional binary computing paradigm, has the potential to enable massively parallel and highly scalable hardware implementations of DCNNs. In this paper, we design and optimize the SC based Softmax Regression function. Experiment results show that compared with a binary SR, the proposed SC-SR under longer bit stream can reach the same level of accuracy with the improvement of 295X, 62X, 2617X in terms of power, area and energy, respectively. Binary SR is suggested for future DCNNs with short bit stream length input whereas SC-SR is recommended for longer bit stream.
Pituitary Corticotroph Ontogeny and Regulation in Transgenic Zebrafish (2003)

We characterized zebrafish proopiomelanocortin (POMC) gene promoter, and sequence analysis revealed that the promoter contains regulatory elements conserved among vertebrate species. To monitor the ontogeny of the pituitary POMC lineage in living vertebrates, we generated transgenic zebrafish expressing green fluorescent protein (GFP) driven by the POMC promoter. Zebrafish POMC-GFP is first expressed asymmetrically as two bilateral groups of cells most anterior to the neural ridge midline at 18-20 h post fertilization (hpf). POMC-GFP-positive cells then fuse into a single-cell mass within the pituitary anlage after 24 hpf and subsequently organize as distinct anterior and posterior domains between 48 and 64 hpf. Immunohistochemical studies with ACTH and alphaMSH antisera showed that POMC-GFP was mainly targeted to both anterior and posterior pituitary corticotrophs, whereas posterior pituitary region melanotrophs did not express GFP. To determine in vivo zebrafish corticotroph responses, dexamethasone (10(-5) m) was added to live embryos, which selectively suppressed POMC-GFP expression in the anterior group of corticotrophs, suggesting a distinct domain that is responsive to glucocorticoid feedback. Transgenic zebrafish with specific POMC-GFP expression in pituitary corticotrophs offers a powerful genetic system for in vivo study of vertebrate corticotroph lineage development.
Thyroid Stimulatory Action of (<i>Z</i>)-Guggulsterone: Mechanism of Action (1988)

(Z)-Guggulsterone, a ketosteroid isolated from the oleoresin of the dry exudate of Commiphora mukul, has been shown to stimulate the thyroid function in rats. This drug is now shown to counteract the thyroid-suppressant activity of a known thyroid inhibitor (carbimazole). This set of observations distinguishes the thyroid stimulatory action of (Z)-guggulsterone from that of the thyroid stimulatory hormone (TSH) of pituitary origin. It is, therefore, concluded that the action of (Z)-guggulsterone is not mediated by the pituitary.
Varenicline for smoking cessation: efficacy, safety, and treatment recommendations (2010)

Smoking is the leading preventable cause of morbidity and mortality in the US, and decreasing smoking prevalence is a public health priority. Patients achieve the greatest success when quit attempts involve behavioral therapy combined with pharmacotherapy. Varenicline is the most recent addition to the pharmacotherapeutic armamentarium for the treatment of tobacco dependence. Varenicline is efficacious and cost-effective. Smoking relapse and adverse treatment-related side effects may decrease medication adherence and patient satisfaction with varenicline. In the clinical setting, varenicline treatment can be optimized by reducing doses in patients who experience intolerable side effects, increasing the dose in partial responders, and providing long-term maintenance therapy for relapse prevention.