gebhart/patrepeval huggingface dataset:
Mefloquine induces ER stress and apoptosis in BRAFi‐resistant A375‐BRAFV600E/NRASQ61K malignant melanoma cells targeting intracranial tumors in a bioluminescent murine model (2022)

Molecularly targeted therapeutics have revolutionized the treatment of BRAF<sup>V600E</sup> -driven malignant melanoma, but the rapid development of resistance to BRAF kinase inhibitors (BRAFi) presents a significant obstacle. The use of clinical antimalarials for the investigational treatment of malignant melanoma has shown only moderate promise, attributed mostly to inhibition of lysosomal-autophagic adaptations of cancer cells, but identification of specific antimalarials displaying single-agent antimelanoma activity has remained elusive. Here, we have screened a focused library of clinically used artemisinin-combination therapeutic (ACT) antimalarials for the apoptotic elimination of cultured malignant melanoma cell lines, also examining feasibility of overcoming BRAFi-resistance comparing isogenic melanoma cells that differ only by NRAS mutational status (BRAFi-sensitive A375-BRAF<sup>V600E</sup> /NRAS<sup>Q61</sup> vs. BRAFi-resistant A375-BRAF<sup>V600E</sup> /NRAS<sup>Q61K</sup> ). Among ACT antimalarials tested, mefloquine (MQ) was the only apoptogenic agent causing melanoma cell death at low micromolar concentrations. Comparative gene expression-array analysis (A375-BRAF<sup>V600E</sup> /NRAS<sup>Q61</sup> vs. A375-BRAF<sup>V600E</sup> /NRAS<sup>Q61K</sup> ) revealed that MQ is a dual inducer of endoplasmic reticulum (ER) and redox stress responses that precede MQ-induced loss of viability. ER-tracker<sup>TM</sup> DPX fluorescence imaging and electron microscopy indicated ER swelling, accompanied by rapid induction of ER stress signaling (phospho-eIF2α, XBP-1s, ATF4). Fluo-4 AM-fluorescence indicated the occurrence of cytosolic calcium overload observable within seconds of MQ exposure. In a bioluminescent murine model employing intracranial injection of A375-Luc2 (BRAF<sup>V600E</sup> /NRAS<sup>Q61K</sup> ) cells, an oral MQ regimen efficiently antagonized brain tumor growth. Taken together, these data suggest that the clinical antimalarial MQ may be a valid candidate for drug repurposing aiming at chemotherapeutic elimination of malignant melanoma cells, even if metastasized to the brain and BRAFi-resistant.
Large-scale purification and preliminary X-ray diffraction studies of human aspartylglucosaminidase (1996)

Aspartylglucosaminidase (AGA) is a lysosomal asparaginase that takes part in the ordered degradation of glycoproteins and a deficiency of which results in a lysosomal accumulation disease aspartylglucosaminuria in human. The mature enzyme consists of 24-kDa and 17-kDa subunits, which are both heterogeneously glycosylated. Activation of the enzyme from a single precursor polypeptide into two subunits is accomplished in the endoplasmic reticulum (ER). The relative lack of this proteolytic capacity in several tested high-producing expression systems has complicated the production of active recombinant enzyme in high quantities, which would be an alternative for purification of this molecule for crystallization. Consequently, the AGA enzyme has to be purified directly from cellular or tissue sources for crystallographic analysis. Here we describe a large-scale purification method to produce milligram amounts of homogeneous AGA from human leukocytes. The purified AGA enzyme represents a heterogeneous pool of molecules not only due to glycosylation, but also heterogeneity at the polypeptide level, as demonstrated here. We were able to isolate a homogeneous peptide pool that was successfully crystallized and preliminary X-ray data collected from the crystals. The crystals diffract well to 2.0 angstroms and are thus suitable for determination of the crystal structure of AGA.
Emulsion-Templated Hierarchically Porous Silica Beads Using Silica Nanoparticles as Building Blocks (2005)

Uniform silica beads were produced using emulsion-templated polymer beads as templates and silica nanoparticles as building blocks. Hybrid silica/alumina and silica/titania beads were also prepared by immersing silica−polymer composite beads or silica beads in the corresponding precursor solutions. Inorganic beads were produced by calcining the polymer−inorganic composites at 520 °C in air. The resulting materials exhibited a hierarchical mesoporous−macroporous structure, with high pore volumes and high surface areas. The mechanical stability of the beads could be enhanced by sintering at 1450 °C under argon or by using sodium silicate as a precursor, but with a concomitant reduction in the total surface area of the materials.
Accurate impedance based fault location algorithm using communication between protective relays (2015)

The reactance method with fault resistance separation has been developed in order to determine the impedance of a fault loop as precisely as possible in a transmission or distribution power system line. This method has commonly been used for impedance calculation in the case of a single phase-to-earth fault in diverse power system protection applications. New developments in this area have shown that the extension of the method to multi-phase faults is not only possible, but also of practical relevance. This research consists of an improvement in the calculation method using data from both the own and the remote end of the line. This approach uses a communication link between two measurement units, e.g. protection relays, which have the advantage of not requiring a precise synchronization with each other. The additional time invariant parameters of the power system, acquired by each device and transferred to the remote end, allow for an exact computation of the fault reactance and fault resistance. In this paper, the derivation of this novel approach, as well as the experimental results in a fault location application are presented.
3-Dimensional graphene-like structures and applications: general discussion (2021)

Stefano Fornasaro opened discussion of the paper by Manuela Melucci: Is the production scalable? Can you comment about reproducibility of the results? Manuela Melucci replied: We used commercial graphene oxide powder (Abalonyx) and commercial hollow fiber cartridges (Plasmart 25,
ChemInform Abstract: A NOVEL NEW HETEROCYCLE FROM THE REACTION OF AZIDE ION WITH 2,3‐DIPHENYLTHIIRENE 1,1‐DIOXIDE (1979)

Abstract Mit Lithiumazid reagiert 2,3‐Diphenyl‐thiiren‐l ,l‐dioxid (I) zu den Folgeprodukten (II)‐(VI), deren Anteile bestimmt werden.
Polymorphic Transition (2016)

This Glossary of Terms Related to Pharmaceutics is needed by practitioners in the field of pharmaceutics as this field fulfills an important and crucial role, different from the roles of other scientific disciplines involved in the drugmaking process. The glossary contains 168 definitions used in pharmaceutics. These are related to various aspects of this discipline, such as: (1) physicochemical characterization of pharmaceutical preparations and the active ingredients they contain; (2) unit operations used in the practice of pharmaceutics; (3) terms related to the various dosage forms; (4) terms related to the various modes and routes of drug delivery; (5) terms used in pharmacokinetics and biopharmaceutics in general; and additional miscellaneous terms. The field of pharmaceutics itself is of a multidisciplinary nature as its practitioners come from a variety of disciplines, such as chemistry or various biological sciences, thus a glossary containing authoritative definitions would be useful for them. The terms used in pharmaceutics are rarely covered by existing glossaries, and in the cases they are, their definitions are often inappropriate for the field of pharmaceutics and require new or modified definitions to better fit the new context.
High Speed And Large Capacity Phase Change Rewritable Disk Recording For Digital Video (1994)

A Phase Change Rewritable (PCR) optical disk has advantages, such as direct overwritability and high speed random access suitable for non-linear video editing, but it is necessary to increase both recording rate and capacity in order to realize high quality and long time digital video storage systems. For this purpose, this paper proposes a new Double-sided 4-head MCAV (DMCAV) method and a Mark Edge Recording (MER) technique with a 30cm diameter PCR disk.
Proposed nomenclature for Pseudallescheria, Scedosporium and related genera (2014)

As a result of fundamental changes in the International Code of Nomenclature on the use of separate names for sexual and asexual stages of fungi, generic names of many groups should be reconsidered. Members of the ECMM/ISHAM working group on Pseudallescheria/Scedosporium infections herein advocate a novel nomenclature for genera and species in Pseudallescheria, Scedosporium and allied taxa. The generic names Parascedosporium, Lomentospora, Petriella, Petriellopsis, and Scedosporium are proposed for a lineage within Microascaceae with mostly Scedosporium anamorphs producing slimy, annellidic conidia. Considering that Scedosporium has priority over Pseudallescheria and that Scedosporium prolificans is phylogenetically distinct from the other Scedosporium species, some name changes are proposed. Pseudallescheria minutispora and Petriellidium desertorum are renamed as Scedosporium minutisporum and S. desertorum, respectively. Scedosporium prolificans is renamed as Lomentospora prolificans.
Compensation of IQ imbalance and transmitter nonlinearities in broadband MIMO-OFDM (2011)

Predistortion techniques are implemented in OFDM systems to improve power amplifier efficiency while keeping in-band and out- of-band distortion at acceptable levels. Predistorter (PD) design for broadband MIMO-OFDM systems introduces several implementation challenges. Coupling effects cannot be avoided in MIMO transceivers where the paths are implemented on the same chipset. Moreover, baseband PDs are affected by imbalances in the IQ modulator. This paper proposes a MIMO-PD that linearizes the power amplifier (PA) response and compensates for both crosstalk and IQ imbalance. Error vector magnitude (EVM) and adjacent channel power ratio (ACPR) results show a significant improvement compared with conventional PD systems.
ChemInform Abstract: Preparation of 3,4‐Fused‐spiro[furan‐5(5H),4′‐piperidin]‐2‐one. (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Parametric compact models for flip chip assemblies (2000)

A parametric thermal compact modeling study of flip chip assemblies is presented. First, a star network of four thermal resistors was found to be optimal for a flip chip with arbitrary geometry and material properties. In a second step several parameters such as thermal underfill conductivity and die size were varied. The effect of these variations on the values of the four thermal resistors of the compact model is investigated. In a third step, a response surface model is derived from these compact models, which gives end-users the possibility of choosing a flip chip with arbitrary geometry and deduce automatically the corresponding thermal compact model. Having the compact model, it is now possible to apply customer specific boundary conditions to this compact model and compute the maximal temperature reached at the junction of the flip chip assembly in the specified environment.
Figure 7 from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities (2023)

&lt;p&gt;&lt;b&gt;A&lt;/b&gt;, Dose–response curves for the PI3K inhibitor alpelisib, the PDGFRA&lt;sup&gt;mutant&lt;/sup&gt; inhibitor avapritinib, the LSD1/HDAC inhibitor corin, the KDM6A/B inhibitor GSK-J4, the MDM2 inhibitor idasanutlin, the NAMPT inhibitor FK866, the FGFR inhibitor infigratinib, and the MEK inhibitor trametinib, tested in mouse tumor-derived GS lines. Cells were treated for 3 days (avapritinib, FK-866, idasanutlin, trametinib) or 6 days (alpelisib, corin, GSK-J4, infigratinib) at the indicated concentrations. The most sensitive and the most resistant cell lines are highlighted with different colors and with dashed vs. solid lines. Means ± SD are plotted from at least &lt;i&gt;n&lt;/i&gt; = 3 replicates. Statistics are summarized in Supplementary Table 7. &lt;b&gt;B&lt;/b&gt;, Kaplan-Meier curves depicting survival of mice orthotopically injected with KPP cells and orally treated for 2 weeks with avapritinib vs. vehicle control. **, &lt;i&gt;P&lt;/i&gt; &lt; 0.01 was calculated using the log-rank Mantel-Cox test. Statistical comparisons are described in Supplementary Table 2. &lt;b&gt;C&lt;/b&gt;, Dose–response curves for alpelisib and trametinib tested against patient-derived cell lines for 6 days at the indicated concentrations. Means ± SD are plotted from at least &lt;i&gt;n&lt;/i&gt; = 3 replicates. Statistics are summarized in Supplementary Table 7. &lt;b&gt;D&lt;/b&gt;, Cell viability assays using mouse GS cells and patient-derived cells following treatment with trametinib, alpelisib, and a combination of both drugs for 6 days at the indicated concentrations. Means ± SD are plotted from at least &lt;i&gt;n&lt;/i&gt; = 3 replicates. ****, &lt;i&gt;P&lt;/i&gt; &lt; 0.0001; **, &lt;i&gt;P&lt;/i&gt; &lt; 0.01 were calculated using ordinary one-way ANOVA. Statistics are summarized in Supplementary Table 7. &lt;b&gt;E&lt;/b&gt;, Left: representative fluorescence images of disseminating GFP&lt;sup&gt;+&lt;/sup&gt; tumor cells 12 days following engraftment, and 4 days following initiation of continuous intracranial delivery of alpelisib and trametinib vs. vehicle control. Scale bar, 1 mm. Right: the extent of dissemination and the size of GFP&lt;sup&gt;+&lt;/sup&gt; tumors following resection at 4 days after treatment. Means ± SD are plotted from at least &lt;i&gt;n&lt;/i&gt; = 3 replicates. *, &lt;i&gt;P&lt;/i&gt; &lt; 0.05 was calculated using the Welch &lt;i&gt;t&lt;/i&gt; test.&lt;/p&gt;
426. Use of Real Time IP-10 Measurements to Identify and Monitor the Dysregulated Immune Response in COVID-19 Patients (2020)

Abstract Background It is estimated that up to 10% of SARS-CoV-2 patients progress from early and pulmonary stages to the most severe stage of illness, which manifests as an extra-pulmonary systemic hyperinflammatory syndrome. Interferon gamma-induced protein 10 (IP-10) is an inflammatory marker that plays a role in the dysregulated host response of COVID-19 infected patients. Clinical monitoring of IP-10 has been restricted in the absence of a rapid diagnostic test. MeMed KeyTM is a novel platform recently cleared to provide IP-10 measurements in 15 minutes. We hypothesized that providing physicians with real time IP-10 measurements would support detection and continuous monitoring of patients with a dysregulated immune response and potentially allow personalized immunomodulation to improve patient outcome. IP-10 levels reflect corticosteroid treatment Methods From 7th April 2020 to 10th May 2020 blood was routinely collected serially from 52 SARS-CoV-2 positive patients hospitalized at a COVID-19 dedicated medical center. A clinical decision support protocol was in place focused on managing viral response, oxygenation and inflammatory state (NCT04389645). Results The median age of the 52 patients was 69, 69% were male, 21% were ventilated, 4 died, 2 due to non-COVID-19 related complications. The most common comorbidities were Diabetes 40% and Hypertension 46%. IP-10 &amp;gt;1000 pg/ml correlated with ICU admission (p&amp;lt; 0.05) and increased COVID-19 severity score (p&amp;lt; 0.01). 19 of the 52 patients had IP-10 &amp;gt;1000 pg/ml, of these 12 were treated with corticosteroids. Monitoring IP-10 within the clinical decision support protocol assisted with personalized corticosteroid regimens with the aim of reducing IP-10 &amp;lt; 1000 pg/ml. The 10 patients that survived exhibited IP-10 levels &amp;gt;1000 pg/ml for 2.6 days on average. In contrast, the 2 patients that died of COVID-19 related complications displayed an average of 7.5 days with IP-10 &amp;gt;1000 pg/ml (p&amp;lt; 0.05). Conclusion Providing physicians with real time measurements of IP-10 in COVID-19 patients proved a useful tool as part of the clinical decision support protocol. Timely identification, monitoring and personalized treatment of COVID-19 patients exhibiting a dysregulated immune response may aid in improving patient outcome. Further studies are warranted. Disclosures Tahel Ilan Ber, MD, MeMed (Employee) Alon Angel, n/a, MeMed (Employee) Lior Kellerman, M.D, MeMed (Employee) Eran Barash, MA, MeMed (Employee) Roy Navon, MSc, MeMed (Employee) Einav Simon, PhD, MeMed (Employee) Noa Avni, PhD, MeMed (Employee) Mary Hainrichson, PhD, MeMed (Employee) Tanya Gottlieb, PhD, MeMed (Employee) Kfir Oved, MD, PhD, MeMed (Employee) Eran Eden, PhD, MeMed (Employee)
Combining Relaying and Reflective Surfaces: Power Consumption and Energy Efficiency Analysis (2022)

Hybrid relaying networks (HRNs) combining both a relay and an intelligent reflective surface (IRS) can lead to enhanced rate performance compared to non-hybrid relaying schemes, where only either an IRS or a relay is utilized. However, utilizing both the relay and the IRS simultaneously results in higher power consumption for the HRNs compared to their counterpart. In this work, we study the required transmit power levels and the energy efficiency (EE) of HRNs utilizing both a half-duplex decode-and-forward (HD-DF) relay and an IRS, and compare their performance with non-hybrid relaying schemes. The impact of the required channel estimation overheads is considered when the reflective beamforming design (RBD) at the IRS is carried out under both instantaneous and statistical channel state information models. Also, the investigation is performed for both slow- and fast-changing environments. In terms of the transmit power requirements, our results show that HRNs can lead to higher power savings if the number of reflective elements at the IRS is not very large. However, non-hybrid relaying schemes are shown to be more energy-efficient, unless the targeted rate is high and the IRS is distant from both transmitter and receiver but within a close proximity to the relay.
Tetracyclines: Light-Activated Antibiotics? (2019)

Tetracyclines are well established antibiotics but show phototoxicity as a side effect. Antimicrobial photodynamic inactivation uses nontoxic dyes combined with harmless light to destroy microbial cells by reactive oxygen species. Tetracyclines (demeclocycline and doxycycline) can act as light-activated antibiotics by binding to bacterial cells and killing them only upon illumination. The remaining tetracyclines can prevent bacterial regrowth after illumination has ceased. Antimicrobial photodynamic inactivation can be potentiated by potassium iodide. Azide quenched the formation of iodine, but not hydrogen peroxide. Demeclotetracycline (but not doxycycline) iodinated tyrosine after light activation in the presence of potassium iodide. Bacteria are killed by photoactivation of tetracyclines in the absence of oxygen. Since topical tetracyclines are already used clinically, blue light activation may increase the bactericidal effect.
Defining optimum electrode arrays for multichannel cochlear prostheses; electrophysiological studies (1978)

Electrophysiological experiments were conducted to determine “optimum” intracochlear locations for bipolar elements of multichannel cochlear prostheses. Brainstem evoked response (BSER) mapping procedures were employed to define the spread of excitation across the auditory nerve array, as a function of current level, evoked by intracochlear electrodes having different configurations and locations. Experiments were conducted in dissected cochleas of anesthetized neomycin-deafened cats. In cochlear regions with few or no dendrites, optimum excitation was effected with longitudinally arrayed electrodes positioned along the medial margin of the spiral lamina. With dendrites present, discrete low-threshold excitation was effected with longitudinally or transversely arrayed electrodes positioned anywhere across the spiral lamina. Excitation was elicited even when few dendrites and ganglion cells survived. We concluded: (1) The bony lamina apparently offers little impedance to brief biphasic electrical pulses; (2) threshold excitation occurs in myelinated portions of dendrites or somata; (3) distance between dendrites or somata and electrodes is a critical factor in effected excitation patterns. [Work supported by NIH Grant ♯NS-11804, NIH Contract ♯N01-NS-7-2367, and Hearing Research, Inc.]
Machined Metal FUSE Array Apertures (2019)

A Frequency-scaled Ultra-wide Spectrum Element (FUSE) antenna aperture is presented that is readily produced as size-scalable modular sub-array tiles via conventional (subtractive) machining of common metal stock, similar to the manufacturing of wideband all-metal Vivaldi flares. Like the Planar Ultra-wideband Modular Antenna (PUMA) array, whose modular aperture production can be automated via commercial printed circuit board (PCB) manufacturing at minimal touch labor, these FUSE apertures can be produced with quick turnaround time at rapid prototyping metal machining shops. The radiator can also be produced via additive manufacturing (3D printing), making this simple design an excellent choice for benchmarking alternative manufacturing techniques. This low-profile ultra-wideband array aperture demonstrates operation from 5 GHz to 21 GHz (4.2:1 VSWR bandwidth), with Voltage Standing Wave Ratios (VSWR) below 2.0 for 45-degree scans in all planes (60-degree scan VSWR <; 2.0, except H-plane scan VSWR <; 3.0) at optimal lattice spacing. Measured results are presented to validate modeling predictions.
Precise Syntheses of Luminescent Polystyrene Microparticles with Encapsulated Organic Dyes for Novel Colloidal Photonic Crystals (2018)

Colloidal crystals (CCs) have received tremendous interest because the highly ordered self-assembly of microparticles leads to the facile fabrication of 3D-photonic crystals. So far, there have been many reports on CC films fabricated with non-luminescent microparticles such as polystyrene (PS) or silica. This situation motivated us to synthesize luminescent PS microparticles by encapsulating organic dyes for the application to novel optoelectronic devices. In this communication, we report the successful preparation of luminescent PS microparticles encapsulating two kinds of organic dyes through emulsion polymerization in the presence of sodium dodecyl sulfate. When the luminescent PS microparticles were synthesized at an appropriate molar concentration of the organic dyes, the uniform CC films exhibited unique optical properties of not only Bragg reflection, but also with efficient white-light emission under illumination with UV light. As an extension of our findings, we could observe clear white-light emission from a flexible CC film of the luminescent PS particles self-assembled on a PET sheet.
ROOTSTOCK-REGULATED GENE EXPRESSION PROFILING IN APPLE TREES REVEALS GENES WHOSE EXPRESSION LEVELS ARE ASSOCIATED WITH FIRE BLIGHT RESISTANCE (2011)

ISHS IX International Symposium on Integrating Canopy, Rootstock and Environmental Physiology in Orchard Systems ROOTSTOCK-REGULATED GENE EXPRESSION PROFILING IN APPLE TREES REVEALS GENES WHOSE EXPRESSION LEVELS ARE ASSOCIATED WITH FIRE BLIGHT RESISTANCE
Sensitivity of serum concentration of cartilage biomarkers to 21‐days of bed rest (2017)

Immobilization independently from injury can cause altered cartilage biomarker concentration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1465-1471, 2018.