gebhart/patrepeval huggingface dataset:
Abstract 764: Rational combination of PF-06463922 (next-generation ALK inhibitor) with PI3K pathway inhibitors overcomes ALKi resistance in EML4-ALK+ NSCLC models (2015)

Abstract Crizotinib (PF-02341066) is a small molecule tyrosine kinase inhibitor of ALK, ROS1 and c-MET that is approved in over 70 countries for the treatment of ALK fusion positive non-small cell lung cancer (ALK+ NSCLC). Crizotinib achieved robust objective response rates of approximately 60% in ALK+ NSCLC and significantly improved progression free survival compared to chemotherapy. The emergence of secondary mutations within the ALK kinase domain or the activation of compensatory signaling pathways in crizotinib and other ALKi refractory tumors prompted searches for next generation of ALKi active against resistance mutations as single agents or in combination with other treatments. Such effort led to our recent discovery of PF-06463922, an ALK/ROS1 inhibitor with greatly improved ALK potency, brain penetration, and broad spectrum activity against all known clinical ALKi-resistant mutations. PF-06463922 is being tested in a Phase I clinical trial in both ALK+ and ROS1 fusion positive NSCLC in treatment naive or ALKi relapsed patients. In our current preclinical study, we explored rational combination strategies to further improve the efficacy of PF-06463922 in ALKi resistant cells or tumors. Our results show that compared to PF-06463922 alone, the combination of this compound with PI3K pathway inhibitors, such as PF-05212384 (PI3K/mTOR), GDC0941 (pan-PI3K) or GDC0032 (beta-sparing) leads to more robust anti-proliferative activity in vitro and greater duration of efficacy in vivo in the ALKi resistant models. These PI3K pathway inhibitors also partially overcome EGF or HGF ligand-induced resistance to PF-06463922. Interestingly, in addition to AKT signaling, both compounds inhibit ERK signaling as well, which may be essential for their enhancement of PF-06463922 cell activity or tumor efficacy in combination settings. Studies are ongoing to identify optimal partners for PF-06463922 combination using isoform selective PI3Ki, AKTi and mTORi. We are also exploring the breadth of efficacy of this combination in overcoming resistance to crizotinib, PF-06463922 or other ALKi. The findings provide important evidence that will help define the clinical development path for PF-06463922. This research effort may ultimately lead to more effective approaches to treat ALKi refractory patients in the clinic. Citation Format: Ping Wei, Ming Qiu, Nathan Lee, Joan Cao, Hui Wang, Konstantinos Tsaparikos, Conglin Fan, Timothy Sargis, Justine Lam, Maruja E. Lira, Goldie Lui, James Hardwick, Valeria Fantin, Paul Rejto, Tod Smeal. Rational combination of PF-06463922 (next-generation ALK inhibitor) with PI3K pathway inhibitors overcomes ALKi resistance in EML4-ALK+ NSCLC models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 764. doi:10.1158/1538-7445.AM2015-764
Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein (2022)

A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up to 37% breadth, that share many characteristics with IOMA, including an average-length CDRL3. Cryo-electron microscopy revealed that ACS101 shares interactions with those observed with other VH1-2 and VH1-46-class bNAbs, but exhibits a unique binding mode to residues in loop D. Analysis of longitudinal sequences from the patient suggests that a transmitter/founder-virus lacking the N276 glycan might have initiated the development of these NAbs. Together these data strengthen the rationale for germline-targeting vaccination strategies to induce IOMA-class bNAbs and provide a wealth of sequence and structural information to support such strategies.
Effect of an organic dye on the ferroelectric phase transition in KH2PO4 (KDP) (2001)

This paper reports on the first measurement of the dielectric permittivity and heat capacity of a KDP crystal doped by Chicago Sky Blue organic dye within a temperature interval including the ferroelectric phase transition at T c =122 K. Similar measurements were made on a pure KDP crystal under the same conditions for the sake of comparison. The heat capacities of the pure and doped crystals were shown to differ substantially within an interval 1 K wide in the vicinity of T c , where an anomaly in the heat capacity of the doped crystal was observed to wash out without producing any change in the temperature position of its maximum. The doping reduces the permittivity in the polar phase markedly. The observed effects are associated with the influence of nonisomorphic defects on the ferroelectric phase transition in a piezoelectric crystal.
Trivalent MDCK cell culture-derived influenza vaccine Optaflu®(Novartis Vaccines) (2009)

Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.
Demonstration of Turbulence-Resilient Self-Homodyne 12-Gbit/s 16-QAM Free-Space Optical Communications Using a Transmitted Pilot Tone (2023)

Free-space optical (FSO) communication links can benefit from recovering both amplitude- and phase-encoded data (e.g., quadrature-amplitude-modulation, QAM) by mixing a local oscillator (LO) with a received data beam in a coherent detector. However, atmospheric turbulence can cause power coupling from a fundamental Gaussian mode of the data beam to higher-order modes, resulting in a significantly degraded mixing efficiency between the data and a fundamental Gaussian LO. Previously, a turbulence-resilient pilot-assisted self-coherent FSO QAM link has been demonstrated by transmitting a frequency-offset Gaussian pilot beam along with the Gaussian data beam. The pilot and data beams experienced similar modal coupling and thus can efficiently mix in a self-heterodyne detector. However, a frequency guard band was used to avoid signal-signal beating interference, thereby reducing the utilization efficiency of the detector's bandwidth. To increase the detector's bandwidth utilization, we experimentally demonstrate in this article a turbulence-resilient 12-Gbit/s 16-QAM FSO link using pilot-assisted self-homodyne detection. The pilot beam is located at the same center optical frequency as the data channel but on an orthogonal polarization. At the receiver, we utilize self-homodyne detection to achieve the efficient mixing of the data and pilot. Compared to self-heterodyne, our approach has ∼2X the utilization efficiency of the detector's bandwidth. Compared to conventional LO-based coherent (homodyne or intradyne) detection, the pilot-assisted self-homodyne link shows up to ∼20-dB improvement of optical-to-electrical mixing efficiency under a turbulence strength of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$2{{\boldsymbol{w}}}_0/ \ {{\boldsymbol{r}}}_0 = \ \sim\! {\boldsymbol{7}}.{\boldsymbol{5}}$</tex-math></inline-formula> . The turbulence resilience of the link is demonstrated with a bit-error rate below the 7% forward error correction limit for 400 different turbulence realizations.
Modulated Thermoelectric Properties of Organic Semiconductors Using Field‐Effect Transistors (2015)

Organic thermoelectric materials, which can transform heat flow into electricity, have great potential for flexible, ultra‐low‐cost and large‐area thermoelectric applications. Despite rapid developments of organic thermoelectric materials, exploration and investigation of promising organic thermoelectric semiconductors still remain as a challenge. Here, the thermoelectric properties of several p‐ and n‐type organic semiconductors are investigated and studied, in particular, how the electric field modulations of the Seebeck coefficient in organic field‐effect transistors (OFETs) compare with the Seebeck coefficient in chemically doped films. The extracted relationship between the Seebeck coefficient ( S ) and electrical conductivity ( σ ) from the field‐effect transistor (FET) geometry is in good agreement with that of chemically doped films, enabling the investigation of the trade‐off relationship among σ , S , carrier concentration, and charging level. The results make OFETs an effective candidate for the thermoelectric studies of organic semiconductors.
Reduced polyalanine-expanded Arx mutant protein in developing mouse subpallium alters Lmo1 transcriptional regulation (2013)

Intellectual disability (ID) is a highly prevalent disorder that affects 1-3% of the population. The Aristaless-related homeobox gene (ARX) is a frequently mutated X-linked ID gene and encodes a transcription factor indispensable for proper forebrain, testis and pancreas development. Polyalanine expansions account for over half of all mutations in ARX and clinically give rise to a spectrum of ID and seizures. To understand how the polyalanine expansions cause the clinical phenotype, we studied mouse models of the two most frequent polyalanine expansion mutations (Arx((GCG)7) and Arx(432-455dup24)). Neither model showed evidence of protein aggregates; however, a marked reduction of Arx protein abundance within the developing forebrain was striking. Examining the expression of known Arx target genes, we found a more prominent loss of Lmo1 repression in Arx((GCG7)/Y) compared with Arx(432-455dup24/Y) mice at 12.5 and 14.5 dpc, stages of peak neural proliferation and neurogenesis, respectively. Once neurogenesis concludes both mutant mouse models showed similar loss of Lmo1 repression. We propose that this temporal difference in the loss of Lmo1 repression may be one of the causes accounting for the phenotypic differences identified between the Arx((GCG)7)and Arx(432-455dup24) mouse models. It is yet to be determined what effect these mutations have on ARX protein in affected males in the human setting.
Synthese, Charakterisierung und Reaktivität von Klavierstuhl‐Rhodium(I)‐Komplexen mit hemilabilen, über eine Aren‐ und eine Phosphanogruppe koordinierenden Liganden (1994)

Welcher Arenligand koordiniert? Einen bislang unbekannten intramolekularen Austausch, bei dem die O ‐gebundenen Arenringe abwechselnd η 6 an das Rh 1 ‐Zentrum binden, beobachtet man zwischen 1 und 1 ′. Dieser Prozeß läuft wahrscheinlich über das Intermediat 2 mit Ether‐Phosphan‐Liganden ab und unterbleibt, wenn das O ‐Atom durch eine CH 2 ‐Gruppe ersetzt wird. magnified image
Global and local view on the electrochemically induced degradation of polyelectrolyte multilayers: from dissolution to delamination (2010)

The electrochemically tailored degradation of polyelectrolyte assemblies holds great promises for the design of inexpensive, easily prepared and precise controlled release systems. However, the conception of such electrochemically responsive platforms for drug or gene delivery requires a detailed understanding of the degradation process of the polyelectrolyte multilayer in which the active species to release are incorporated. To this end, we assess here the influence of an applied electric potential on different polyelectrolyte systems, combining global and local investigation techniques. In situ atomic force microscopy allows us to evidence morphological changes at the nano- and micro-scale, while the investigation at a larger scale by optical waveguide lightmode spectroscopy brings complementary information relating not only to material release into the bulk solution, but also to ion migration and swelling. Weak and highly hydrated poly(L-lysine)/hyaluronic acid assemblies with thicknesses up to several hundreds of nanometre continuously dissolve upon electrochemical trigger. However, stronger and more compact films made of poly(allylamine hydrochloride) and poly(styrene sulfonate) dissolve only if their thickness is of a few tens of nanometres, while thicker films delaminate from the electrode. Additional results obtained with composite films combining both polyelectrolyte systems allow us to present mechanisms based on the continuous formation of protons at the electrode surface due to water electrolysis which fully describe the dissolution and the delamination processes. In addition, the study also reveals a novel approach for the release of free-standing polyelectrolyte membranes, which is of great interest for the development of mechanical sensors, separation membranes, or micromechanical devices.
To Seal or Not To Seal (2019)

When an object impacts the free surface of a liquid, it ejects a splash curtain upwards and creates an air cavity below the free surface. As the object descends into the liquid, the air cavity eventually closes under the action of hydrostatic pressure (deep seal). In contrast, the surface curtain may splash outwards or dome over and close, creating a surface seal. In this paper we experimentally investigate how the splash curtain dynamics are governed by the interplay of cavity pressure difference, gravity, and surface tension and how they control the occurrence, or not, of surface seal. Based on the experimental observations and measurements, we develop an analytical model to describe the trajectory and dynamics of the splash curtain. The model enables us to reveal the scaling relationship for the dimensionless surface seal time and discover the existence of a critical dimensionless number that predicts the occurrence of surface seal. This scaling indicates that the most significant parameter governing the occurrence of surface seal is the velocity of the airflow rushing into the cavity. This is in contrast to the current understanding which considers the impact velocity as the determinant parameter.
Preoperative angiographic diagnosis of primary sarcoma of the pulmonary artery. (1982)

Primary neoplasms of the pulmonary artery are extremely rare and usually are not recog- nized until autopsy. We present a case in which the correct preoperative diagnosis was established by cardiac catheterization. The hemodynamic and angiographic findings of sarcoma of the pulmonary artery are distinct and should not be overlooked in the evaluation of right ventricular outflow tract obstruction.
Tetragonal cobalt(III) complexes containing tetradentate macrocyclic amine ligands with different degrees of unsaturation (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTetragonal cobalt(III) complexes containing tetradentate macrocyclic amine ligands with different degrees of unsaturationSusan C. Jackels, Keith. Farmery, E. Kent. Barefield, Norman J. Rose, and Daryle H. BuschCite this: Inorg. Chem. 1972, 11, 12, 2893–2901Publication Date (Print):December 1, 1972Publication History Published online1 May 2002Published inissue 1 December 1972https://pubs.acs.org/doi/10.1021/ic50118a008https://doi.org/10.1021/ic50118a008research-articleACS PublicationsRequest reuse permissionsArticle Views872Altmetric-Citations76LEARN 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
ChemInform Abstract: Evaluation of Amino Acid Based Linkers in Potent Macrocyclic Inhibitors of Farnesyl‐Protein Transferase. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
Observation in atomic fluorescence of the absolute phase of a microwave field (2003)

Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text G. C. Cardoso, P. Pradhan, and S. M. Shahriar, "Observation in atomic fluorescence of the absolute phase of a microwave field," in Frontiers in Optics, OSA Technical Digest (CD) (Optica Publishing Group, 2003), paper PDP6. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Preliminary mutational analysis of the human kinin B2receptor for nonpeptide antagonist ligands recognition (2002)

FR173657, LF16,0335, and LF16,0687 are nonpeptide antagonists, endowed with high affinity and selectivity for the human kinin B 2 receptor. The kinin B 2 receptor belongs to the family of G-protein-coupled receptors with seven transmembrane (TM) helices. In the present study, we aimed, through computer-assisted modeling and mutagenesis, to identify residues in the human B 2 receptor (hB 2 R) amino acid sequence that are involved in nonpeptide antagonist binding in order to build up experimental data as a first step towards a molecular model of nonpeptide ligands binding site. Fourteen amino acid residues within the TM segments were mutated to alanine. The wild type and mutant receptors were stably expressed in Chinese hamster ovary (dhfr) cells and tested for their ability to bind agonist ([ 3 H]bradykinin) and peptide antagonist ([ 3 H]MEN11270) radioligands. The affinity of nonpeptide ligands was determined by heterologous competition experiments using the above radioligands. We found that some mutations in TM2 (W86A) and TM7 (Y295A, N297A) impair the binding affinity of the three nonpeptide antagonists. On the other hand, some mutated residues in TM3 (S117A) and TM6 (W256A) reduce the affinity of LF16,0335 and LF16,0687 only. Results are discussed in order to build up a hypothesis for the likely different interactions of various nonpeptide ligands with the B 2 receptor.Key words: binding, bradykinin B 2 receptor, G-protein-coupled receptor, mutagenesis, nonpeptide.
Confined Monolayer Ag As a Large Gap 2D Semiconductor and Its Momentum Resolved Excited States (2022)

2D materials have intriguing quantum phenomena that are distinctively different from their bulk counterparts. Recently, epitaxially synthesized wafer-scale 2D metals, composed of elemental atoms, are attracting attention not only for their potential applications but also for exotic quantum effects such as superconductivity. By mapping momentum-resolved electronic states using time-resolved and angle-resolved photoemission spectroscopy (ARPES), we reveal that monolayer Ag confined between bilayer graphene and SiC is a large gap (>1 eV) 2D semiconductor, consistent with ab initio GW calculations. The measured valence band dispersion matches the GW quasiparticle band structure. However, the conduction band dispersion shows an anomalously large effective mass of 2.4 m<sub>0</sub>. Possible mechanisms for this large enhancement in the "apparent mass" are discussed.
Identification of a Vibrational Frequency Corresponding to H-atom Translocation in Hypericin¶ (2001)

Using time-resolved infrared spectroscopy, ab initio quantum mechanical calculations and synthetic organic chemistry a region in the infrared spectrum of triplet hypericin has been found between 1400 and 1500 cm-1 corresponding to the translocation of the hydrogen atom between the enol and the keto oxygens, O...H...O. This result is discussed in the context of the photophysics of hypericin and of eventual measurements to observe directly the excited-state H-atom transfer.
RESOLFT imaging and writing with a photochromic GFP (2012)

Keywords: Super-resolution ; Fluorescence microscopy ; Photo-switchable proteins Reference EPFL-TALK-176407 Record created on 2012-04-25, modified on 2017-05-10
AKMA Support in Multi SIM User Equipment (2019)

Multi SIM User Equipment (UE) can have more than one physical slot for Universal Integrated Circuit Card (UICC). The eUICC is an embedded version of the UICC, which cannot be physically removed from the communication device. Currently, 3rd Generation Partnership Project (3GPP) is working on developing Authentication and Key Management for Applications (AKMA), with which user can bootstrap authentication towards application server from his mobile subscription. We consider the scenario that may become common in devices with Multi SIM and eUICC, in which one subscription is used for primary services such as voice and data, and another subscription is used for AKMA services. In this scenario, the purpose is to use AKMA services simultaneously and without interrupting primary services. There are existing requirements for Multi SIM and eUICC, which restrain this scenario from being successful. The solution that we propose includes arrangements and adaptations, in order to provide secure and uninterrupted services of both primary and AKMA services.
A finite element method for the study of solidification processes in the presence of natural convection (1986)

Abstract A new numerical technique has been developed for the analysis of two‐dimensional transient solidification processes in the presence of time‐dependent natural convection in the melt. The method can cope with irregular, transient morphologies of the solid—liquid interface using a new Galerkin formulation for the energy balance on the solid—liquid interface. The finite element solution to the Galerkin formulation yields the displacement of individual nodes on the solid—liquid interface. The displacement of the nodes is expressed by uncoupled components in the x and y directions. The fluid flow problem was solved using a ‘penalty’ formulation. Numerical experiments were performed for Rayleigh numbers as high as 10 6 to demonstrate the method and to indicate the effect of natural convection on the solid—liquid interface morphology.