gebhart/patrepeval huggingface dataset:
DYRK1B as therapeutic target in Hedgehog/GLI-dependent cancer cells with Smoothened inhibitor resistance (2016)

A wide range of human malignancies displays aberrant activation of Hedgehog (HH)/GLI signaling, including cancers of the skin, brain, gastrointestinal tract and hematopoietic system. Targeting oncogenic HH/GLI signaling with small molecule inhibitors of the essential pathway effector Smoothened (SMO) has shown remarkable therapeutic effects in patients with advanced and metastatic basal cell carcinoma. However, acquired and de novo resistance to SMO inhibitors poses severe limitations to the use of SMO antagonists and urgently calls for the identification of novel targets and compounds.Here we report on the identification of the Dual-Specificity-Tyrosine-Phosphorylation-Regulated Kinase 1B (DYRK1B) as critical positive regulator of HH/GLI signaling downstream of SMO. Genetic and chemical inhibition of DYRK1B in human and mouse cancer cells resulted in marked repression of HH signaling and GLI1 expression, respectively. Importantly, DYRK1B inhibition profoundly impaired GLI1 expression in both SMO-inhibitor sensitive and resistant settings. We further introduce a novel small molecule DYRK1B inhibitor, DYRKi, with suitable pharmacologic properties to impair SMO-dependent and SMO-independent oncogenic GLI activity. The results support the use of DYRK1B antagonists for the treatment of HH/GLI-associated cancers where SMO inhibitors fail to demonstrate therapeutic efficacy.
EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas (2015)

EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.
Design and fabrication of double-chirped mirrors (1997)

We present an analytic design method for the reproducible fabrication of double-chirped mirrors to achieve simultaneously a high reflectivity and dispersion compensation over an extended bandwidth compared with those of standard quarter-wave Bragg mirrors. The mirrors are fabricated by ion beam sputtering. Use of these mirrors in a Ti:sapphire laser leads to 6.5-fs pulses directly out of the laser. The method can also be applied to the design of chirped-fiber gratings and general optical filters.
Amino Acid Sequence Analysis, Gene Construction, Cloning, and Expression of Gelonin, a Toxin Derived from <i>Gelonium multiflorum</i> (1995)

The plant toxin gelonin is an extremely potent inhibitor of protein synthesis, similar in action to ricin. The mature protein primary sequence was obtained using conventional sequencing techniques. Gelonin was found to be composed of 258 amino acids and contains 21 lysine residues. This toxin shares approximately 33% sequence homology with trichosanthin and ricin A chain. A 774 bp synthetic gene encoding gelonin was synthesized and expressed in E. coli. Recombinant gelonin (approximately 28 kD) expression was monitored and demonstrated by western analysis. Purification and functional activity studies demonstrated that this protein behaves identically to that of the natural product. Recombinant gelonin (RG) thus joins a growing list of recombinant toxins currently available for use in the construction of recombinant immunotoxins composed of gelonin fused to binding domains of antibodies, growth factors, or other cytokines.
Planar He plasma jet: plasma bullets formation, 2D bullets concept and imaging (2018)

Applications of dielectric barrier discharge (DBD) based atmospheric pressure plasma jets are often limited by the relatively small area of treatment due to their 1D configuration. This letter describes the first results demonstrating generation of 2D plasma bullets and 2D plasma jets permitting fast treatment of large targets. Imaging of pulsed DBD in He and ionization wave propagation along the dielectric surface show that DBD evolution starts with formation of transient anode glow, and only then continues with development of cathode-directed streamers. The anode glow can propagate as an ionization wave along the dielectric surface outside of the discharge gap. We show that plasma bullets propagation is not limited to 1D geometry (tubes), and can be organized in a form of a planar plasma jet, or other 2D (or even 3D) shapes.
99mTc(CO)3(NTA): A 99mTc Renal Tracer with Pharmacokinetic Properties Comparable to Those of 131I-OIH in Healthy Volunteers (2010)

Objectives—Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical 99mTc(CO)3-nitrilotriacetic acid, 99mTc(CO)3(NTA), were essentially identical to those of 131I ortho-iodohippuran (131I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these two tracers in healthy volunteers. Methods—99mTc(CO)3(NTA) was prepared with commercially available NTA and a commercially available IsoLink kit (Covidien) and isolated by reversed-phased high-performance liquid chromatography. Approximately 74 MBq (2.0 mCi) of 99mTc(CO)3(NTA) were coinjected with 9.25 MBq (250 μCi) of 131I-OIH in nine volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3–90 min after injection using the single-injection, two-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 minutes were determined. Results—There was no difference in the plasma clearances of 99mTc(CO)3(NTA) and 131I-OIH, 475 ± 105 mL/min versus 472 ± 108 mL/min, respectively. The plasma protein binding and red cell
A spread-spectrum technique for high-capacity mobile communications (1978)

A spread-spectrum technique for cellular high-capacity mobile communications is described and some results from an analytic study are summarized. The technique uses a very large set of frequency-hopped signals which are designed for minimal mutual interference. No synchronization of the mobile units is required, and each user is permanently assigned his own signal, which serves as an identifying signal and as a carrier for the biphase-modulated digital message. The spectral efficiency of the spread-spectrum system is analyzed and compared with the efficiencies of developmental FM/channel reuse schemes currently under construction in the U.S. and Japan. It is concluded that even with relatively simple speech digitization schemes, the efficiency of the spread-spectrum scheme may exceed those of the narrow-band schemes by a factor of almost five. More ambitious bit-rate-reducing speech digitization methods could improve still further on these figures. Additional benefits of the spread-spectrum scheme include immunity from fading and interference, more consistent speech quality, simpler system control algorithms, and more flexible blocking properties under overload conditions.
Fast Production of High-Quality Graphene via Sequential Liquid Exfoliation (2015)

A novel and practical approach of exfoliating graphite into graphene uses a sequence of flow and sonication on graphite suspensions. Graphite sediment after intense mixing is found to be altered, graphite having curled-up edges, which increases its sensitivity to ultrasound. Quadrupled graphene yield is achieved through introducing flow pretreatment.
Optimal node repositioning for tolerating node failure in wireless sensor actor network (2010)

Wireless sensor and actor networks (WSANs) usually operate in harsh environment and thus become susceptible to breakage in connectivity due to the failure of one or multiple actor nodes. The positions of some of these actors are critical to the sustainability of inter-node communications. Specifically, some node failures may cause the network to partition into disjoint segments. Given that WSANS are deployed in remote areas, restoring connectivity through self reconfiguring the network topology becomes the most preferred solution. This paper investigates the optimal actor repositioning for restoring connectivity after one or multiple node fail. In particular, the problem is formulated as an integer linear program such that every node can reach every other node in the network while maximizing network coverage and minimizing the distance that an actor ought to travel.
Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory (2017)

Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.
Spectrally controlled interferometry for improved radius of curvature measurement (2019)

Spectrally controlled interferometry promises to increase accuracy at a reduced cost for radius of curvature measurements for spherical optics by removing the catseye position during measurement and exploiting the inherent ability to measure absolute distances without mechanical compensation.
Forward Osmosis Membranes – A Review: Part II (2018)

Forward osmosis (FO) is a technical term describing the natural phenomenon of osmosis: the transport of water molecules across a semipermeable membrane by osmotic pressure from a feed solution (FS) to a draw solution (DS). The diluted DS is then reconcentrated to recycle the draw solutes as well as to produce purified water. As the driving force is only the osmotic pressure difference between two solutions, meaning that there is no need to apply an external energy, this results in low fouling propensity of membrane and minimization of irreversible cake forming, which are the main problems controverted by membrane applications, especially in biological treatment systems (e.g., FO membrane bioreactor (FO-MBR)). The purpose of the book chapter is to bring an overview on the FO membrane manufacturing, characterizing and application area at laboratory or full scales. This book chapter is published in two parts. In the second part, which appears here, characterization of mass transport in FO membranes, fouling mechanisms and foulants on FO membranes in naturally asymmetric structure and application areas of FO membranes in the literature are mentioned. Cutting-edge technologies on FO studies are comprehensively reviewed and following major and minor titles are stated truly on the new technologies.
Design and Fabrication of an Extreme Temperature Sensing Optical Probe using Silicon Carbide Technologies (2007)

For the first time, to the best of our knowledge, designed and fabricated is an extreme temperature optical sensor using a single crystal silicon carbide (SiC) optical chip packaged within a sintered SiC hollow tube. The fabricated assembly forms the critical frontend probe of the proposed hybrid wireless-wired optical sensor used for measuring >1000degC temperatures within hot gas chambers such as in coal-fired power generation systems. Initial probe test experiments show the required water-tight chip-end probe sealing and the desired retro-reflected optical interferograms required for temperature-based signal processing.
Hybrid multiplier for <i>GF</i> (2 <sup> <i>m</i> </sup> ) defined by some irreducible trinomials (2004)

A trade-off between performance and area is important to design an efficient hardware structure for arithmetic operations in GF(2m). Proposed is a hybrid multiplier for GF(2m) with an irreducible trinomial, which can be constructed in variable structures depending on such a performance area trade-off.
Targeting Aldose Reductase for the Treatment of Cancer (2011)

It is strongly established by numerous studies that oxidative stress-induced inflammation is one of the major causative agents in a variety of cancers. Various factors such as bacterial, viral, parasitic infections, chemical irritants, carcinogens are involved in the initiation of oxidative stress-mediated inflammation. Chronic and persistent inflammation promotes the formation of cancerous tumors. Recent investigations strongly suggest that aldose reductase [AR; AKR1B1], a member of aldo-keto reductase superfamily of proteins, is the mediator of inflammatory signals induced by growth factors, cytokines, chemokines, carcinogens etc. Further, AR reduced product(s) of lipid derived aldehydes and their metabolites such as glutathionyl 1,4-dihydroxynonanol (GS-DHN) have been shown to be involved in the activation of transcription factors such as NF-κB and AP-1 which transcribe the genes of inflammatory cytokines. The increased inflammatory cytokines and growth factors promote cell proliferation, a main feature involved in the tumorigenesis process. Inhibition of AR has been shown to prevent cancer cell growth in vitro and in vivo models. In this review, we have described the possible association between AR with oxidative stress- and inflammation- initiated carcinogenesis. A thorough understanding of the role of AR in the inflammation -associated cancers could lead to the use of AR inhibitors as novel chemotherapeutic agents against cancer.
Direct Radical Polymerization of Vinyl Ethers: Reversible Addition–Fragmentation Chain Transfer Polymerization of Hydroxy-Functional Vinyl Ethers (2016)

Unprecedented controlled radical vinyl polymerization (CRP) of vinyl ethers using reversible addition–fragmentation chain transfer (RAFT) polymerization is reported. In order to overcome the challenge of direct radical polymerization of vinyl ethers, commercial hydroxy-functional vinyl ethers such as 2-hydroxyethyl vinyl ether (HEVE) were subjected to free radical polymerization, generating vinyl polymers without polyacetals obtained by self-polyaddition polymerization. In the case of bulk polymerization using a nonacidic azo-initiator such as dimethyl 2,2′-azobis(2-methylpropionate), conventional free radical vinyl polymerization occurred with sufficiently high number-average molecular weight. For example, poly(HEVE) was produced from the corresponding HEVE monomer with Mn = 26 400 in high yield, ≥75%. The resulting polymer was nearly identical to the polymer prepared by living cationic polymerization using the protected monomers except for the steric regularity (meso dyads are 51% and 67% for radical and cationic polymerizations, respectively). Furthermore, cyanomethyl methyl(phenyl)carbamodithioate was found to be an efficient RAFT agent, enabling the CRP of hydroxy-functional vinyl ethers. Under the polymerization conditions, poly(HEVE) macromolecular chain transfer agent (macro-CTA) was prepared. The kinetic studies of RAFT polymerization showed a linear increase of the molecular weight, with up to 50% monomer conversion and relatively low polydispersities (Mw/Mn < 1.38). In addition, chain extension experiments including block copolymerization with vinyl acetate and N-vinylpyrrolidone were demonstrated using the resulting poly(HEVE) macro-CTA to confirm the “livingness” of the poly(HEVE).
Exploring the structure of a real-time, arbitrary neural artistic stylization network (2017)

In this paper, we present a method which combines the flexibility of the neural algorithm of artistic style with the speed of fast style transfer networks to allow real-time stylization using any content/style image pair. We build upon recent work leveraging conditional instance normalization for multi-style transfer networks by learning to predict the conditional instance normalization parameters directly from a style image. The model is successfully trained on a corpus of roughly 80,000 paintings and is able to generalize to paintings previously unobserved. We demonstrate that the learned embedding space is smooth and contains a rich structure and organizes semantic information associated with paintings in an entirely unsupervised manner.
Lorentz force actuation of a heated atomic force microscope cantilever (2012)

We report Lorentz force-induced actuation of a silicon microcantilever having an integrated resistive heater. Oscillating current through the cantilever interacts with the magnetic field around a NdFeB permanent magnet and induces a Lorentz force that deflects the cantilever. The same current induces cantilever heating. With AC currents as low as 0.2 mA, the cantilever can be oscillated as much as 80 nm at resonance with a DC temperature rise of less than 5 °C. By comparison, the AC temperature variation leads to a thermomechanical oscillation that is about 1000 times smaller than the Lorentz deflection at the cantilever resonance. The cantilever position in the nonuniform magnetic field affects the Lorentz force-induced deflection, with the magnetic field parallel to the cantilever having the largest effect on cantilever actuation. We demonstrate how the cantilever actuation can be used for imaging, and for measuring the local material softening temperature by sensing the contact resonance shift.
The chimeric mouse-human anti-CD4 Fab 13B8.2 expressed in baculovirus inhibits both antigen presentation and HIV-1 promoter activation (2001)

The anti-CD4 mAb 13B8.2, directed against the CDR3-like loop of the D1 domain of CD4, inhibits signal transduction pathways leading to both T cell activation and HIV replication. VH9/DSP2/JH2 and Vkappa12-13/Jkappa2 rearrangements, corresponding to genes encoding the heavy and light chain variable regions of the 13B8.2 mAb, were inserted into baculovirus cassettes upstream from pre-installed human Fdgamma1 and Ckappa genes, respectively. After expression in insect cells, a complete correctly-processed Fab was secreted into the culture medium; it was protein-G immunopurified with a yield of 5 mg/L. The chimeric Fab 13B8.2 showed anti-CD4 binding activity with an affinity value of 3.3 nM and recognized the same region on the CDR3-like loop as the parental mAb. The mouse-human Fab inhibited IL2 secretion following antigen presentation and displayed a strong capacity to prevent HIV-1 promoter activation. Taken together, these results indicate that the chimeric Fab retained a major part of the parental 13B8.2 mAb properties and suggest that it might be a valuable therapeutic tool.
Topical Phenytoin in Neuralgic Pain, Peripheral Modulation of Central Sensitization: Two Case Reports (2017)

We herewith describe a topical formulation of phenytoin with a clear analgesic effect in localized neuropathic pain: in post herpetic neuralgia and trigeminal neuralgia. Such topical analgesic effect for phenytoin has not yet been described in literature. We have developed various topical phenytoin formulations and identified a stable cream base in which we compounded a range of concentrations of phenytoin up to 10%. We will present two cases supporting the analgesic effect of phenytoin cream in neuralgic pain, and discuss the putative mechanism of action of phenytoin as a topical analgesic. The essence of both cases is that, apparently, it is possible to down-regulate central sensitization processes via the modulation (inhibition) of peripheral input. This hypothesis was brought forward in 2013 based on neurophysiological data, and our clinical data seem to also support this important chapter in pain treatment. Thus, topical analgesia, in our case based on phenytoin, can play an important role in multimodal therapy of chronic neuropathic pain, related to central sensitization states.
Categorization of multiple sclerosis relapse subtypes by B cell profiling in the blood (2014)

Our data indicate actively ongoing B cell-mediated immunity against brain antigens in a subset of MS patients that may be causative of clinical relapses and provide new diagnostic and therapeutic options for a subset of patients.
Characterization of Alisertib (MLN8237), an Investigational Small-Molecule Inhibitor of Aurora A Kinase Using Novel <i>In Vivo</i> Pharmacodynamic Assays (2011)

Alisertib is a selective and potent inhibitor of AAK. The novel methods of measuring Aurora A pathway inhibition and application of tumor imaging described here may be valuable for clinical evaluation of small-molecule inhibitors.
Sortase‐Catalyzed Initiator Attachment Enables High Yield Growth of a Stealth Polymer from the C Terminus of a Protein (2013)

Conventional methods for synthesizing protein/peptide-polymer conjugates, as a means to improve the pharmacological properties of therapeutic biomolecules, typically have drawbacks including low yield, non-trivial separation of conjugates from reactants, and lack of site- specificity, which results in heterogeneous products with significantly compromised bioactivity. To address these limitations, the use of sortase A from Staphylococcus aureus is demonstrated to site-specifically attach an initiator solely at the C-terminus of green fluorescent protein (GFP), followed by in situ growth of a stealth polymer, poly(oligo(ethylene glycol) methyl ether methacrylate) by atom transfer radical polymerization (ATRP). Sortase-catalyzed initiator attachment proceeds with high specificity and near-complete (≈95%) product conversion. Subsequent in situ ATRP in aqueous buffer produces 1:1 stoichiometric conjugates with >90% yield, low dispersity, and no denaturation of the protein. This approach introduces a simple and useful method for high yield synthesis of protein/peptide-polymer conjugates.