gebhart/patrepeval huggingface dataset:
Abstract LB-031: Deciphering distinct roles of RASA2 in melanomagenesis (2017)

Abstract Melanoma is the deadliest form of human skin cancer. The incidence of melanoma continues to rise. Recent advances in knowledge of melanoma genetics, genomics and biology has led to an optimistic view of the therapeutic outlook for melanoma patients. We analyzed sequence data from &amp;gt;500 melanoma genomes/exomes to identify novel tumor suppressor genes in melanoma. RASA2 was identified as the most highly somatically mutated novel tumor suppressor gene. RASA2 was mutated in 5% of melanomas and deleted in an additional 16.4% of cases. RASA2 is a GTPase Activating Protein (GAP) that regulates RAS; which is one of the most highly mutated oncogenes in melanoma but drugs targeting RAS have as yet shown poor efficacy. The role of RASA2 has not been investigated in melanoma. NF1, which encodes another RAS- specific GAP, was found to be frequently mutated in melanoma. Interestingly, mutations in RASA2 and NF1 co-occur in the same patients with high frequency. We plan to elucidate the roles of RASA2 in melanomagenesis and to understand why RASA2 and NF1 mutations co-occur despite the fact that both proteins are RasGAPs. Ras includes three isoforms: NRas, KRas and HRas. Our preliminary data show that RASA2 is more specific to NRAS and that NF1 is more specific to KRAS and HRAS. This finding highlights the existence of a paradigm of cooperativity in which combined loss of multiple negative regulators (RASA2 and NF1) of the RAS pathway is required for melanoma development. Therefore, this type of enhancement of RAS signaling is possibly selected for in some melanomas. We will apply a proteomic screen using BioID to identify RASA2 and NF1 binding partners to provide insights into the functional effects and consequences of alterations in RASA2 and NF1. We expect that these studies will not only identify the cellular components that contribute to the Ras signaling pathway but will also identify potential novel therapeutic targets. Citation Format: Rand Arafeh, Nouar Qutob, Rafi Rafi Emmanuel, Jason Madore, Abdel Elkahloun, James S. James S. Wilmott, Jared J. Gartner, Antonella Di Pizio, Ron Rotkopf, Ken Dutton-Regester, Victoria Hill, Antonia Pritchard, Jimmy C. Lin, Steven A Rosenberg, Javed Khan, Shifra Ben-Dor, Masha Y. Masha Y. Niv, Igor Ulitsky, Graham J Mann, Richard A. Scolyer, Nicholas K. Hayward, Yardena Samuels. Deciphering distinct roles of RASA2 in melanomagenesis [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 LB-031. doi:10.1158/1538-7445.AM2017-LB-031
Multifunctional Gold Nanoparticles in Drug Delivery Systems (2020)

Gold (Au) is among the most precious of metals in existence for both its everlasting luster and its recently recognized utility in the field of nanomedicine. This chapter aims to report on the present state of multifunctional gold nanoparticles (AuNPs) in nanomedicine and focus on the design of such constructs for use in drug delivery applications. It explains the synthesis of the AuNP base, conjugation of imaging and targeting agents, and the applications of these multifunctional AuNPs in drug delivery systems. The amount of information regarding the synthesis methods for AuNPs has grown exponentially since the time of Faraday. Although the syntheses of AuNPs under various conditions have been well documented, many difficulties exist in producing AuNPs on a large scale. AuNPs display an incredible capacity to perform multiple functions at the nanoscale and at the same time remain relatively biologically inert and responsive. These characteristics lend themselves ideally to nanopharmaceutical applications, particularly in the form of precise and efficient nanomedicine.
Hybrid Fluorescent-Magnetic Polymeric Particles for Biomedical Applications (2014)

Submicron magnetic polymeric particle (MPP) and/or Janus magnetic polymeric particle (JMPP) were successfully prepared via the miniemulsion polymerization of styrene (St)/acrylic acid (AA) monomers consisting of superparamagnetic iron oxide nanoparticles (IONPs) coated with oleic acid. Since the particle nucleation occurs primarily within the monomer droplet, not only the size of particle could be controlled at the beginning but also its morphology was manipulated by using different types of initiator. The MPPs with homogeneous distribution of IONPs (41%) in P(St-DVB-AA) were obtained with using potassium persulfate (KPS) as initiator and divinyl benzene (DVB) as crosslinking agent. To obtain anisotropic JMPP, an oil-soluble initiator 2,2-azobis (2-isobutyronitrile) was used instead. The controllable phase separation between P(St-AA) and the encapsulated IONPs caused the stable spherical Janus particles containing IOPNs (15%) located on one side of polymer particle. Both MPPs and JMPPs could be easily separated by an external magnet. The MPPs were functionalized with chitosan (CS) acting as spacer and then chemical immobilized with fluorescein isothiocyanate (FITC) to produce fluorescent-MPPs. When applying as imaging device for cancer cells labeling i.e., HeLa, cells, results showed that MPPs/CS-FITC could be located inside cells with low cytotoxicity.
FCGR2A and FCGR3A Genotypes Correlate with Farletuzumab Response in Patients with First-Relapsed Ovarian Cancer Exhibiting Low CA125 (2017)

Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha and elicits an anti-tumor response via immune effector activity. Recent studies from a global phase 3 trial in ovarian cancer patients treated with carboplatin/taxane plus farletuzumab found that the tumor-produced CA125 protein can suppress farletuzumab function via perturbing its engagement to the activating Fc-γ receptors CD32a (FCGR2A) and CD16a (FCGR3A). Previous reports have indicated that naturally occurring polymorphisms in both of these receptors may play a role in their ability to engage therapeutic antibodies and elicit an optimal immune response via antibody-dependent cellular cytotoxicity (ADCC). In light of the importance of farletuzumab ADCC function for optimal tumor cell killing, we evaluated the frequency of FCGR2A-131H/R and FCGR3A-158V/F polymorphisms in 461 consenting patients from this global clinical study and their association with clinical outcome to placebo versus farletuzumab treatment. Here, we show that farletuzumab has enhanced binding to FCGR3A-158V high-affinity receptor and has an enhanced clinical outcome in patients with low baseline CA125 levels and at least 1 high-affinity allele of FCGR2A or FCGR3A.
Taurine reabsorption by a carrier interacting with furosemide in short and long Henle's loops of rat nephrons (1997)

Taurine is net reabsorbed in the proximal convolution by Cl- -stimulated Na+ symport specific for beta-amino acids but not in later nephron segments. However, large unidirectional taurine transport takes place there. To investigate unidirectional taurine reabsorption, we comicroinfused [3H]taurine and [14C]inulin into late proximal (LP), early distal (ED), and late distal (LD) tubule segments, as well as into the tips of long loops of Henle (LLH) of rats in vivo, and determined fractional reabsorption of [3H]taurine (FR) in the ipsilateral urine. FR (9 micromol/l taurine) was 80-93 (LP), 16 (ED), and 8% (LD). At 26 mmol/l taurine, FR decreased to 13 (LP) and 6% (ED). FR also decreased when Na+ or Cl- was absent or furosemide (5 x 10(-5) mol/l) was added. Bumetanide (5 x 10(-5) mol/l) had no effect, whereas aniline-2-sulfonic acid (ASA) inhibited. During LLH microinfusion, FR was 55% at 66 micromol/l and 17% at 228 micromol/l and was again inhibited by furosemide and ASA but not by bumetanide. [14C]taurine reabsorption from microperfused proximal convolutions was not influenced by furosemide. Chronic water diuresis did not affect taurine reabsorption in short Henle's loops. We conclude that taurine can enter cells of the distal nephron from the lumen by an Na+- and partly Cl- -dependent carrier with which C alpha,beta-substituted taurine (ASA) and C alpha,beta- and N-substituted beta-alanine (furosemide) directly interact. Thus proximal and distal taurine carriers seem to be different.
Developing a JAK Inhibitor for Targeted Local Delivery: Ruxolitinib Cream (2021)

Named after the two-faced Roman god of doorways, Janus kinases (JAKs) represent a class of tyrosine kinases. The JAK signaling pathway is pivotal for the downstream signaling of inflammatory cytokines, including interleukins, interferons, and multiple growth factors. This article provides an overview of the JAK pathway and signaling, its significance in immune-mediated dermatologic diseases and the development of a targeted, localized option of a selective JAK inhibitor, ruxolitinib cream. In the early 1990s, various discovery and clinical development programs were initiated to explore pharmaceutical inhibition of the JAK-STAT pathway. Incyte Corporation launched a strategy to identify molecules suitable for both topical as well as oral delivery. Ruxolitinib was designed as a molecule with low nanomolar potency selective for JAK1 and 2 enzymes, but without significant inhibition of non-JAK kinases, as well as physicochemical properties for both topical and oral administration. An oil-in-water emulsified ruxolitinib cream formulation was developed for topical application and was studied in multiple immune-mediated dermatologic diseases including psoriasis, alopecia areata, atopic dermatitis and vitiligo. Ruxolitinib cream represents a novel, JAK1/2 selective therapy that can be delivered directly to the skin to treat a number of cytokine-driven, inflammatory dermatoses.
Crystal structures of N-[4-(trifluoromethyl)phenyl]benzamide and N-(4-methoxyphenyl)benzamide at 173 K: a study of the energetics of conformational changes due to crystal packing (2022)

As a part of our study of the syntheses of aryl amides, the crystal structures of two benzamides were determined from single-crystal X-ray data at 173 K. Both crystal structures contain mol-ecular units as asymmetric units with no solvent in the unit cells. Crystal structure I, <b>TFMP</b>, is the result of the crystallization of <i>N</i>-[4-(tri-fluoro-meth-yl)phen-yl]benzamide, C<sub>14</sub>H<sub>10</sub>F<sub>3</sub>NO. Crystal structure II, <b>MOP</b>, is composed of <i>N</i>-(4-meth-oxy-phen-yl)benzamide, C<sub>14</sub>H<sub>13</sub>NO<sub>2</sub>, units. <b>TFMP</b> is triclinic, space group <i>P</i> , consisting of two mol-ecules in the unit cell related by the center of symmetry. <b>MOP</b> is monoclinic, space group <i>P</i>2<sub>1</sub>/<i>c</i>, consisting of four mol-ecules in the unit cell. Both types of mol-ecules contain three planar regions; a phenyl ring, an amide planar region, and a <i>para</i>-substituted phenyl ring. The orientations of these planar regions within the asymmetric units are compared to their predicted orientations, in isolation, from DFT calculations. The aryl rings are tilted approximately 60° with respect to each other in both experimentally determined structures, as compared to 30° in the DFT results. These conformational changes result in more favorable environments for N-H⋯O hydrogen bonding and aryl ring π-stacking in the crystal structures. Inter-molecular inter-actions were examined by Hirshfeld surface analysis and qu-anti-fied by calculating mol-ecular inter-action energies. The results of this study demonstrate that both hydrogen bonding and dispersion are essential to the side-by-side stacking of mol-ecular units in these crystal structures. Weaker dispersion inter-actions along the axial directions of the mol-ecules reveal insight into the melting mechanisms of these crystals.
Synthesis and Properties of Water-Soluble Gold Colloids Covalently Derivatized with Neutral Polymer Monolayers (2002)

Citrate-capped gold nanoparticles as well as planar gold surfaces can be efficiently grafted with a covalently attached polymer monolayer a few nanometers thick, by simple contact of the metal surface with dilute aqueous solutions of hydrophilic polymers that are end-capped with disulfide moieties, as shown by UV/vis absorption, dynamic light scattering, and surface plasmon resonance studies. The hydrophilic polymer-coated gold colloids can be freeze-dried and stored as powders that can be subsequently dissolved to yield stable aqueous dispersions, even at very large concentrations. They allow for applying filtrations, gel permeation chromatography, or centrifugation. They do not suffer from undesirable nonspecific adsorption of proteins while allowing the diffusion of small species within the hydrogel surface coating. In addition, specific properties of the original hydrophilic polymers are retained such as a lower critical solution temperature. The latter feature could be useful to enhance optical responses of functionalized gold surfaces toward interaction with various substrates.
PowerPC 970 in 130 nm and 90 nm technologies (2004)

A 64 b PowerPC microprocessor is introduced in 130 nm and redesigned in 90 nm SOI technology. PowerPC 970 implements a SIMD instruction set with 512 kB L2 cache. It runs at 2.0 GHz with a 1.0 GHz bus in 130 nm. The 90 nm design features PowerTune for rapid frequency and power scaling and electronic fuses.
Supplementary Figures and Tables from Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection (2023)

&lt;p&gt;Supplementary Figure 1. Principal Components Analysis (PCA) of global microRNA expression. Supplementary Figure 2. Significantly differentially expressed microRNAs between current and former smokers (q&lt;0.01). Supplementary Table 1. Patient demographics stratified by cancer status. Supplementary Table 2. Smoking associated microRNAs (p&lt;0.05) Supplementary Table 3. Gender associated microRNAs (p&lt;0.05) Supplementary Table 4. Age associated microRNAs (p&lt;0.05) Supplementary Table 5. Pack-years (PY) associated microRNAs (p&lt;0.05) Supplementary Table 6. Cancer associated microRNAs (p&lt;0.05) Supplementary Table 7. Biomarker performance in the test set (* significant increase in AUC compared to mRNA biomarker p&lt;0.05; â€ ROC-curve Operating Point set to 90% sensitivity in the training set).&lt;/p&gt;
Oligo(cyclohexylidene) oximes and derivatives as probe molecules for long-range substituent effects on 13C NMR chemical shifts (1996)

For a series of rodlike aliphatic oximes (1–4) the influence of the oxime substituent on the 13C NMR chemical shifts has been studied. Various 2D NMR techniques were applied for the unequivocal assignment of their 1H and 13C resonances. For bicyclohexylidene oximes 1–2 long-range substituent effects on the 13C NMR chemical shifts of aliphatic carbon atoms of the six-membered rings due to the presence of the oxime group are discernible up to positions six carbon–carbon bonds distant from the iminyl carbon! The 13C NMR data obtained for bicyclohexyl oximes 3–4 reveal that in this series the effect is limited to carbon atoms which are five bonds distant from the iminyl carbon. The observed differences between the two series is attributed to the presence of an olefinic double bond in 1–2, which becomes polarized by the electric field of the oxime substituent.
Activation of p16 Gene Silenced by DNA Methylation in Cancer Cells by Phosphoramidate Derivatives of 2′-Deoxyzebularine (2008)

We report herein the application of the phosphoramidate ProTide technology to improve the metabolism of the DNA methytransferase inhibitor, zebularine (Z). Zebularine is a riboside that must undergo a complex metabolic transformation before reaching the critical 2'-deoxyzebularine 5'-triphosphate (dZTP). Because 2'-deoxyzebularine (dZ) is not phosphorylated and therefore inactive, the ProTide strategy was employed to bypass the lack of phosphorylation of dZ and the inefficient reduction of zebularine 5'-diphosphate by ribonucleotide-diphosphate reductase required for zebularine. Several compounds were identified as more potent inhibitors of DNA methylation and stronger inducers of p16 tumor suppressor gene than zebularine. However, their activity was dependent on the administration of thymidine to overcome the potent inhibition of thymidylate synthase (TS) and deoxycytidine monophosphate (dCMP) deaminase by dZMP, which deprives cells of essential levels of thymidine. Intriguingly, the activity of the ProTides was cell line-dependent, and activation of p16 was manifest only in Cf-Pac-1 pancreatic ductal adenocarcinoma cells.
Toward the optoelectronic ULSI: drivers and barriers (2004)

We describe the state of the art in optoelectronic component integration, and the current degree of commercial deployment of integrated optoelectronics as dictated by the balance of market pull and technology push. We also present the long-term outlook for optoelectronic integration, including the drivers and barriers that set the roadmap toward the optoelectronic ULSI. We discuss an optoelectronic integration platform that utilizes organic and inorganic materials for the hybrid integration of passive and active optical elements.
Toward Theoretical Guidance for Two Common Questions in Practical Cross-Validation based Hyperparameter Selection (2023)

We show, to our knowledge, the first theoretical treatments of two common questions in cross-validation based hyperparameter selection: ➀ After selecting the best hyperparameter using a held-out set, we train the final model using all of the training data - since this may or may not improve future generalization error, should one do this? ② During optimization such as via SGD (stochastic gradient descent), we must set the optimization tolerance ρ - since it trades off predictive accuracy with computation cost, how should one set it? Toward these problems, we introduce the hold-in risk (the error due to not using the whole training data), and the model class mis-specification risk (the error due to having chosen the wrong model class) in a theoretical view which is simple, general, and suggests heuristics that can be used when faced with a dataset instance. In proof-of-concept studies in synthetic data where theoretical quantities can be controlled, we show that these heuristics can, respectively, ➀ always perform at least as well as always performing retraining or never performing retraining, ② either improve performance or reduce computational overhead by 2× with no loss in predictive performance. * Full version: https://arxiv.org/abs/2301.05131
Induction of Morphological and Biochemical Apoptosis following Prolonged Mitotic Blockage by Halichondrin B Macrocyclic Ketone Analog E7389 (2004)

E7389, a macrocyclic ketone analog of the marine natural product halichondrin B, currently is undergoing clinical trials for cancer. This fully synthetic agent exerts its highly potent in vitro and in vivo anticancer effects via tubulin-based antimitotic mechanisms, which are similar or identical to those of parental halichondrin B. In an attempt to understand the impressive potency of E7389 in animal models of human cancer, its ability to induce apoptosis following prolonged mitotic blockage was evaluated. Treatment of U937 human histiocytic lymphoma cells with E7389 led to time-dependent collection of cells in the G2-M phase of the cell cycle, beginning as early as 2 h and becoming maximal by 12 h. Increased numbers of hypodiploid events were seen beginning at 12 h, suggesting initiation of apoptosis after prolonged E7389-induced mitotic blockage. The identity of hypodiploid events as apoptotic cells under these conditions was confirmed by two additional morphologic criteria: green to orange/yellow shifts on acridine orange/ethidium bromide staining, and cell surface annexin V binding as assessed by flow cytometry. Several biochemical correlates of apoptosis also were seen following E7389 treatment, including phosphorylation of the antiapoptotic protein Bcl-2, cytochrome c release from mitochondria, proteolytic activation of caspase-3 and -9, and cleavage of the caspase-3 substrate poly(ADP-ribose) polymerase (PARP). In LNCaP human prostate cancer cells, treatment with E7389 also led to generation of hypodiploid cells, activation of caspase-3 and -9, and appearance of cleaved PARP, indicating that E7389 can activate cellular apoptosis pathways under anchorage-independent and -dependent cell culture conditions. These results show that prolonged mitotic blockage by E7389 can lead to apoptotic cell death of human cancer cells in vitro and can provide a mechanistic basis for the significant in vivo anticancer efficacy of E7389.
Linear oligopeptides, 77. The effect of the insertion of a proline residue on the solid‐state conformation of host peptides (1981)

Abstract The conformational properties of two series of monodispersed, chemically and optically pure, PEG The following abbreviations have been used in the text: PEG, poly(ethylene glycol); ‐NHPEG, “amino‐PEG”; ‐NHPEG‐M, “amino‐PEG” monomethyl ether; NPS, o ‐nitrophenylsulfenyl; t ‐Boc, tert ‐butoxycarbonyl; Z, benzyloxycarbonyl; Met, methionine; Pro, proline; OBzl, benzyloxy; OMe, methoxy; OEt, ethoxy; NHEt, ethylamino; Glu, glutamic acid; IR, infrared; MeOH, methanol; TFE, 2,2,2‐trifluoroethanol. ‐bound linear host oligopeptides of the general formula \documentclass{article}\pagestyle{empty}\begin{document}$ t{\rm - Boc\rlap{--} (L - Met\rlap{--} )}_n {\rm NHPEG} $\end{document} and \documentclass{article}\pagestyle{empty}\begin{document}$ t{\rm - Boc\rlap{--} [L - Glu(OBl)\rlap{--} ]}_n {\rm NHPEG - M} $\end{document} containing a single guest L ‐Pro residue at different positions in the main chain have been investigated in the solid state using IR absorption. The corresponding N‐deblocked peptides have also been examined. The incorporation of a L ‐Pro residue in a central position of a β‐conformation appears to induce the onset of a structural irregularity characterized by IR absorption bands in the vicinity of 3 325 cm −1 and 1 575 cm −1 .
The Influence of Standing Waves on Cleaning with a Megasonic Nozzle (2009)

A non uniform sound field distribution can be a problem in a megasonic cleaning system, since a higher sound intensity can cause damage, while areas exposed to a lower intensity will be insufficiently cleaned. These non uniformities can be the result of sound field reflection, leading to standing waves, and the interference related to the near field. In a single wafer tool with a transducer facing the wafer a small height difference will have a large impact on the cleaning efficiency if standing waves are present. Here we study the impact of the wafer transducer height in a cleaning system using a megasonic nozzle above a rotating wafer.
Characterizing the population structure and genetic diversity of maize breeding germplasm in Southwest China using genome-wide SNP markers (2016)

For the panel covered most of widely used inbred lines in Southwest China, this work representatively not only illustrates the foundation and evolution trend of maize breeding resource as a theoretical reference for the improvement of heterosis, but also provides plenty of information for genetic researches such as genome-wide association study and marker-assisted selection in the future.