gebhart/patrepeval huggingface dataset:
Protein catabolism in fibroblasts cultured from patients with mucolipidosis II and other lysosomal disorders (1993)

Protein catabolism in fibroblasts cultured from the skin of normal individuals and of patients with mucolipidosis II (I-cell disease) and several other lysosomal storage diseases was examined by metabolic labelling with [3H]leucine and following the fate of radioactive proteins in pulse-chase experiments. In mucolipidosis II cells, overall protein degradative rates were found to be distinctly lower than in normal control cells. To distinguish lysosomal from non-lysosomal degradation, labelling experiments were carried out in the presence and absence of 10 mM NH4Cl, an inhibitor of lysosomal function. It was found that mucolipidosis II fibroblasts exhibited a markedly reduced rate of lysosomal protein degradation, whereas the rate of nonlysosomal degradation appeared normal. Serum and amino acid starvation led to a marked increase in lysosomal protein degradation in normal cells, but had only a minimal effect on that in mucolipidosis II fibroblasts. The specific activities of cathepsins B, H and L were profoundly diminished in all mucolipidosis II cell lines tested. Lysosomal protein degradation in a mucolipidosis III cell line was impaired to a similar degree as in mucolipidosis II cells, whereas it was decreased to a lesser extent in fibroblasts from patients with mucopolysaccharidoses I and VI, galactosialidosis and GM1-gangliosidosis. We conclude that fibroblasts from patients with mucolipidosis II and III have a severely compromised capacity for endogenous lysosomal protein degradation that appears to result from multiple cathepsin deficiency. This lysosomal defect is likely to have pathophysiological consequences.
Functional Central Nicotinic Acetylcholine Receptor Antagonism by Systemic Administration of Tinuvin 770 (BTMPS) (2005)

Tinuvin 770 (BTMPS) is a non-competitive, use-dependent antagonist of nicotinic acetylcholine receptors (nAChRs). The drug is highly lipid soluble and as such it has the potential to act within the brain. Presently the ganglionic blocking drug mecamylamine is used almost exclusively to block central nAChRs upon peripheral administration. These experiments were designed to confirm the nAChR antagonism effectiveness of BTMPS in both peripheral (ganglionic stimulation) and central (locomotor activity and thermal nociceptive sensitivity) nicotinic system in vivo. BTMPS inhibited the expression of the pressor response produced by i.v. injection of the ganglionic stimulant DMPP in anesthetized rats. The inhibition dose-response profile appeared to be biphasic with the maximal inhibition occurring after administration of the 0.48 mg/kg dose of BTMPS. In rats acclimated to the test apparatus, nicotine increased different measures of locomotor activity, particularly at the 0.75 mg/kg dose. BTMPS pretreatment significantly inhibited the nicotine-induced increase in motor behaviors, again with a biphasic dose-response relationship. Lastly, nicotine elicited an antinociceptive response in rats (hot plate test). BTMPS almost completely blocked the antinociceptive responses to 1 and 1.5 mg/kg nicotine. On its own, BTMPS failed to decrease blood pressure and to decrease the nociceptive threshold. The drug also generally failed to alter locomotor activity. The use-dependent aspect of BTMPS-induced inhibition of nAChRs was evident in the drug's greater effectiveness in the presence of the highest doses of nicotine. Therefore, BTMPS can be considered as an alternative to or as a confirmatory drug for mecamylamine when inhibition of central nicotinic receptors is required.
Applied Optimal Control (2018)

This best-selling text focuses on the analysis and design of complicated dynamics systems. CHOICE called it ""a high-level, concise book that could well be used as a reference by engineers, applied mathematicians, and undergraduates. The format is good, the presentation clear, the diagrams instructive, the examples and problems helpful...References and a multiple-choice examination are included.
Ultrasonographically guided surgical approach to liver tumours involving the hepatic veins close to the caval confluence (2006)

IOUS allowed sparing of the liver parenchyma without tumour recurrence in most patients with a tumour involving a hepatic vein at the caval confluence, avoiding more extensive hepatectomy or vascular reconstruction.
Electrochemical Activation of the Tetrazine Ligation for Surface Modification (2018)

Our lab has been interested in developing conjugation reactions that can be triggered by electrochemical potential. Such reactions could have application in the functionalization of independently addressable electrode arrays. These include past effortsusing the electrochemistry to locally generate copper+1 to trigger the well-known copper catalyzed azide alkyne cycloaddition. Our lab has been interested in an alternative bioorthogonal reaction, the tetrazzini ligation, as a versatile coupling tool. Unlike “click” chemistry, the tetrazine ligation does not have a redox active catalyst. However, one of the reactive components (the tetrazine) is redox active and can be reduced to a dihydrotetrazine, preventing cycloaddition. Through this manner, bioconjugation can be controlled electrochemically. I will summarize our findings in this area and discuss applications.
Modeling the inter-electrode capacitances of Si CoolMOS transistors for circuit simulation of high efficiency power systems (2010)

The CoolMOS™ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> transistor is a power MOSFET type device that utilizes a “super-junction” embedded within its drift region in order to improve the trade-off between on-resistance and breakdown voltage. The super-junction results in unique inter-electrode capacitance characteristics that require an advanced modeling approach to accurately represent switching performance. This paper describes a new compact circuit simulator model for the CoolMOS™ transistor and demonstrates the model performance using the Saber <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">†</sup> simulator for a 650 V, 60 A device. The model is suitable for implementation in the Saber simulator that accurately describes all three inter-electrode capacitances (i.e., gate-drain, gate-source, and drain-source capacitances) for the full operating range of the device. The model is derived using the actual charge distribution within the device rather than assuming a lumped charge or one-dimensional charge distribution. Simulation results show excellent agreement with measurement results in contrast to previous modeling approaches used for this device. The compact model developed in this work is going to be utilized in the design of a high efficiency soft-switching inverter for electric vehicle motor drives and a high efficiency bidirectional DC-DC converter at zero-voltage switching (ZVS) operation.
Speech discrimination based on multiscale spectro-temporal modulations (2004)

A novel approach for content based audio classification is presented based on multiscale spectro-temporal modulation features extracted using a model of auditory cortex. The task is to discriminate speech from non-speech which consists of animal vocalizations, music and environmental sounds. Generalization of the system to signals in high level of additive noise and reverberation is evaluated and compared to two existing approaches. The results demonstrate the advantages of the auditory model over the other two systems, especially at low SNR and high reverberation.
Mid-wavelength infrared avalanche photodetector with AlAsSb/GaSb superlattice (2021)

In this work, a mid-wavelength infrared separate absorption and multiplication avalanche photodiode (SAM-APD) with 100% cut-off wavelength of ~ 5.0 µm at 200 K grown by molecular beam epitaxy was demonstrated. The InAsSb-based SAM-APD device was designed to have electron dominated avalanche mechanism via the band structure engineered multi-quantum well structure based on AlAsSb/GaSb H-structure superlattice and InAsSb material in the multiplication region. The device exhibits a maximum multiplication gain of 29 at 200 K under -14.7 bias voltage. The maximum multiplication gain value for the MWIR SAM-APD increases from 29 at 200 K to 121 at 150 K. The electron and hole impact ionization coefficients were derived and the large difference between their value was observed. The carrier ionization ratio for the MWIR SAM-APD device was calculated to be ~ 0.097 at 200 K.
Synthesis of Os2(CO)8(.mu.-CHCH3) from a geminal ditriflate and its reversible carbonylation to a ketene-bridged diosmacycle (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Os2(CO)8(.mu.-CHCH3) from a geminal ditriflate and its reversible carbonylation to a ketene-bridged diosmacycleR. Morris. Bullock, Robert T. Hembre, and Jack R. NortonCite this: J. Am. Chem. Soc. 1988, 110, 23, 7868–7870Publication Date (Print):November 1, 1988Publication History Published online1 May 2002Published inissue 1 November 1988https://pubs.acs.org/doi/10.1021/ja00231a043https://doi.org/10.1021/ja00231a043research-articleACS PublicationsRequest reuse permissionsArticle Views199Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Management of patients with high-risk and advanced prostate cancer in the Middle East: resource-stratified consensus recommendations (2019)

This is the first regional consensus on prostate cancer management from the Middle East. The following recommendations will be useful to urologists and oncologists practicing in all areas with limited access to specialist multi-disciplinary teams, diagnostic modalities and treatment resources.
Imaging fibroblast activation protein alpha expression using 89Zr-DFO-F19 mAb (2014)

1038 Objectives Fibroblast activation protein alpha (FAP) is a serine protease that is overexpressed on neuroepithelial and sarcoma tumors (1-2). The goal of this work was to characterize 89Zr-DFO-F19 mAb, a PET radiopharmaceutical that specifically targets FAP, and evaluate its potential as a PET and Cerenkov Luminescence Imaging (CLI) agent for FAP positive tumors in vivo. Methods 89Zr-DFO-F19 was prepared according to standard protocols (3). The immunoreactivity and Ka of 89Zr-DFO-F19 was determined using the Lindmo Method and the U87mg cell line, which demonstrates the highest endogenous FAP expression among available cancer cell lines. Biodistribution, CLI, small animal PET/CT and autoradiography studies were conducted in mice bearing FAP+ U87mg tumors using known procedures. Results 89Zr-DFO-F19 was radiolabeled in high radiochemical purity and with a specific activity of 158.3 ± 1.6 MBq/mg (4.28 ± 0.04 mCi / mg, n = 6). CLI imaging of female nude mice implanted with U87mg tumors in the flank revealed substantially greater uptake in tumors than in other tissues such as liver, kidney, muscle or bone. Small animal PET/CT image analysis revealed excellent tumor accumulation of the radiopharmaceutical at 48 h p.i., which was reduced upon the administration of blockade [tumor: (non-block vs. block: SUV; p value): 2.39±0.45 vs. 1.73 ±0.11; 0.03]. Autoradiography and histological analysis of tissue slices demonstrated the colocalization of radioactivity with areas of increased FAP expression and validated both the CLI and small animal PET/CT results. Conclusions 89Zr-DFO-F19 represents a novel PET radiopharmaceutical for FAP positive tumors. CLI imaging confirmed localization within tumor xenografts but not in FAP negative tissues. This was corroborated by biodistribution, small animal PET/CT and autoradiography studies. Research Support DoD W81XWH-13-1-0125
Human and sylvatic Trypanosoma cruzi infection in California. (1985)

In August 1982, a 56-year-old woman from Lake Don Pedro, California, developed acute Chagas' disease (American trypanosomiasis). She had not traveled to areas outside the United States with endemic Chagas' disease, she had never received blood transfusions, and she did not use intravenous drugs. Trypanosoma cruzi cultured from the patient's blood had isoenzyme patterns and growth characteristics similar to T. cruzi belonging to zymodeme Z1. Triatoma protracta (a vector of Trypanosoma cruzi) infected with T. cruzi were found near the patient's home, a trypanosome resembling T. cruzi was cultured from the blood of two of 19 ground squirrels (Spermophilus beecheyi), and six of 10 dogs had antibody to T. cruzi. A serosurvey of three groups of California residents revealed antibody to T. cruzi by complement fixation in six of 237 (2.5 per cent) individuals living near the patient and in 12 of 1,706 (0.7 per cent) individuals living in a community 20 miles northeast of the patient's home, but in only one of 637 (0.2 per cent) blood donors from the San Francisco Bay area. This is the first case of indigenously acquired Chagas' disease reported from California and the first case recognized in the United States since 1955. This investigation suggests that transmission of sylvatic Trypanosoma cruzi infection to humans occurs in California but that Chagas' disease in humans is rare.
National Patterns of Angiotensin-Converting Enzyme Inhibitor Use in Congestive Heart Failure (1997)

The low rates of use of ACE inhibitors in patients with CHF and the wide variations in their use suggest a need to move beyond clinical trials and focus attention on modifying physician practices.
Escherichia coliK99 pili are composed of one subunit species (1981)

Peer Reviewed
Centrosymmetric molecules for second harmonic generation (1996)

The requirement of a non‐centrosymmetric structure for second harmonic generation (SHG) was until recently assumed necessarily to apply to te smallest building block, the molecule. However, non‐centrosymmetric aggregates of centrosymmetric molecules can exist, and their SHG properties are considered here. Derivatives of squaraines are taken as examples. Finally, the role of intermolecular charge transfer in Langmuir–Blodgett film‐forming materials for SHG—both within the monolayers and across the boundary—is discussed.
Structure-Based Identification of Small Molecule Binding Sites Using a Free Energy Model (2006)

We separately have shown that the maximal druglike affinity of a given binding site on a protein can be calculated on the basis of the binding-site structure alone by using a desolvation-based free energy model along with the notion that druglike ligands fall into certain physiochemical property ranges. Here, we present an approach where we reformulate the calculated druggability affinity as an additive free energy to facilitate the searching of whole protein surfaces for druglike binding sites. The highest-scoring patches in many cases represent known ligand-binding sites for druggable targets, but not for difficult targets. This approach differs from other approaches in that it does not simply identify pockets with the greatest volume but instead identifies pockets that are likely to be amenable to druglike small-molecule binding. Combining the method with a functional residue prediction method called SCA (statistical coupling analysis) results in the prediction of potentially druggable allosteric binding sites on p38alpha kinase.
MarkIt: Community Play and Computation to Generate Rich Location Descriptions through a Mobile Phone Game (2010)

The capture and description of the numerous 'places' found in urban environments could enable the deployment of seamless mobile and location-aware social navigation tools. Unfortunately, we are limited in our approaches to systematically capture place data at the requisite level of granularity or how to obtain labeling consensus. We explored this issue through 'research through design', developing and deploying the MarkIt mobile phone game, which aimed to engage a community of users in place description. In this paper, we present our design rationale and the game's design. We then highlight how key innovations instantiated in MarkIt resulted in rapid data generation of both images and location related labels.
Rheological Characterization and Coagulation Casting of Al 2 O 3 –Nano Zirconia Suspensions (2007)

The rheological behavior of electrosterically dispersed aqueous suspensions composed of submicrometer alumina and nano zirconia particles in different ratios and solids contents (from 34 to 40 vol%) has been studied during in situ coagulation casting. Glucono‐δ‐lactone was used as the coagulant to achieve destabilization of the ceramic suspensions by acidifying the suspension so that the pH became close to the isoelectric point for both powders. The effects of the lactone content (from 0.5 to 6.7 wt%) and the solids loading on the rheological parameters (dynamic and static measurements) during the coagulation process were studied. Dynamic measurements showed an increasing elastic modulus, G′, with time and lactone content (viz. 180 and 340 kPa for 6.7 wt% lactone addition after 40 and 60 min, respectively, and 57.3 kPa for 0.5 wt% lactone after 60 min), suggesting the formation of stronger green bodies at higher additions and longer times. The conditions were optimized to yield homogeneous green samples with a uniform nanozirconia distribution and densities between 58% and 60% of the theoretical. These were subsequently sintered to yield composites with a final density up to 97%.
On alphabetic presentations of Clifford algebras and their possible applications (2009)

In this paper, we address the problem of constructing a class of representations of Clifford algebras that can be named “alphabetic (re)presentations.” The Clifford algebra generators are expressed as m-letter words written with a three-character or a four-character alphabet. We formulate the problem of the alphabetic presentations, deriving the main properties and some general results. At the end, we briefly discuss the motivations of this work and outline some possible applications.
DFT-Based Studies on the Jahn−Teller Effect in 3d Hexacyanometalates with Orbitally Degenerate Ground States (2007)

The topology of the ground-state potential energy surface of M(CN)(6) with orbitally degenerate (2)T(2g) (M = Ti(III) (t(2g)(1)), Fe(III) and Mn(II) (both low-spin t(2g)(5))) and (3)T(1g) ground states (M = V(III) (t(2g)(2)), Mn(III) and Cr(II) (both low-spin t(2g)(4))) has been studied with linear and quadratic Jahn-Teller coupling models in the five-dimensional space of the epsilon(g) and tau(2g) octahedral vibrations (Tg[symbol: see text](epsilon(g)+tau(2g)) Jahn-Teller coupling problem (T(g) = (2)T(2g), (3)T(1g))). A procedure is proposed to give access to all vibronic coupling parameters from geometry optimization with density functional theory (DFT) and the energies of a restricted number of Slater determinants, derived from electron replacements within the t(2g)(1,5) or t(2g)(2,4) ground-state electronic configurations. The results show that coupling to the tau(2g) bending mode is dominant and leads to a stabilization of D(3d) structures (absolute minima on the ground-state potential energy surface) for all complexes considered, except for [Ti(CN)(6)](3-), where the minimum is of D(4h) symmetry. The Jahn-Teller stabilization energies for the D3d minima are found to increase in the order of increasing CN-M pi back-donation (Ti(III) < V(III) < Mn(III) < Fe(III) < Mn(II) < Cr(II)). With the angular overlap model and bonding parameters derived from angular distortions, which correspond to the stable D(3d) minima, the effect of configuration interaction and spin-orbit coupling on the ground-state potential energy surface is explored. This approach is used to correlate Jahn-Teller distortion parameters with structures from X-ray diffraction data. Jahn-Teller coupling to trigonal modes is also used to reinterpret the anisotropy of magnetic susceptibilities and g tensors of [Fe(CN)(6)](3-), and the (3)T(1g) ground-state splitting of [Mn(CN)(6)](3-), deduced from near-IR spectra. The implications of the pseudo Jahn-Teller coupling due to t(2g)-e(g) orbital mixing via the trigonal modes (tau(2g)) and the effect of the dynamic Jahn-Teller coupling on the magnetic susceptibilities and g tensors of [Fe(CN)(6)](3-) are also addressed.
Abstract 24: HMBD001, a novel anti-ErbB3 antibody with a unique mechanism of action, effectively inhibits tumor growth in pre-clinical models of ErbB3+ solid tumors (2017)

Abstract Gastric cancer is the second highest cause of cancer mortality in Asia. Over-expression of ErbB3, a cell surface RTK, occurs in ~60% of mGC patients where it is significantly associated with poorer survival. Ligand binding to ErbB3 triggers heterodimerization and downstream signaling through Akt. Neutralizing antibodies that inhibit ligand binding show poor efficacy in clinical trials, likely due to high levels of ligand independent activation in many tumor types. Directly inhibiting heterodimerization could be more effective, however, current methods of antibody isolation offer limited control over the site of antibody binding and, therefore, mechanism of action, requiring extensive screening of antibodies and posing significant challenges to identifying suitable candidates for therapeutic development. Hummingbird Bioscience has used its proprietary Rational Antibody Development Platform for the design and development of novel therapeutic antibodies against ErbB3. Computational sequence and structural analyses predicted highly specific surface epitopes, with strong antigenicity and good safety profiles, where antibody binding would inhibit dimerization. Subsequently, Hummingbird’s directed evolution mouse immunization strategy efficiently isolated monoclonal antibodies that bound with low nM (Kd &amp;lt; 5nM) affinity to these epitopes on native folded ErbB3. Furthermore, these mAbs showed ELISA cross-reactivity to ErbB3 in model organisms (mouse, rat, monkey) but no binding to other EGFR family proteins. Antibody HMBD001 was found to strongly inhibit the phosphorylation of ErbB3 and decrease downstream signaling through the Akt pathway (90% decrease in p-ErbB3 and 60% decrease in p-AKT observed at 24 hrs) resulting in the inhibition of tumor cell proliferation in models of ErbB3+ gastric cancer (over 90% inhibition of NCI-N87 proliferation after 5 days) and breast cancer (up to 85% inhibition of BT474 proliferation after 5 days). In mouse NCI-N87 gastric cancer CDX models, weekly doses of HMBD001 achieved greater than 90% inhibition of tumor growth (at 25 days) with no observable adverse toxicity. The first in-human trial of HMBD001 is planned for 2018. Citation Format: Jerome D. Boyd-Kirkup, Dipti Thakkar, Piers J. Ingram. HMBD001, a novel anti-ErbB3 antibody with a unique mechanism of action, effectively inhibits tumor growth in pre-clinical models of ErbB3+ solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 24. doi:10.1158/1538-7445.AM2017-24