gebhart/patrepeval huggingface dataset:
Antibody-Drug Conjugates Targeting Tumor-Specific Mucin Glycoepitopes (2022)

Finding the ideal epitope to target is a key element for the development of an antibody-drug conjugate (ADC). To maximize drug delivery to tumor cells and reduce side effects, this epitope should be specific to cancer cells and spare all normal tissue. During cancer progression, glycosylation pathways are frequently altered leading to the generation of new glycosylation patterns selective to cancer cells. Mucins are highly glycosylated proteins frequently expressed on tumors and, thus, ideal presenters of altered glycoepitopes. In this review, we describe three different types of glycoepitopes that are recognized by monoclonal antibodies (mAb) and, therefore, serve as ideal scaffolds for ADC; glycan-only, glycopeptide and shielded-peptide glycoepitopes. We review pre-clinical and clinical results obtained with ADCs targeting glycoepitopes expressed on MUC1 or podocalyxin (Podxl) and two mAbs targeting glycoepitopes expressed on MUC16 or MUC5AC as potential candidates for ADC development. Finally, we discuss current limits in using glycoepitope-targeting ADCs to treat cancer and propose methods to improve their efficacy and specificity.
Molecular Aspect of Energy Transfer from Tb3+ to Eu3+ in the Polyoxometalate Lattices: An Approach for Molecular Design of Rare-Earth Metal-Oxide Phosphors (2006)

The exploitation of mixed heteronuclear rare-earth-element-containing polyoxometalates to probe the multipolar nature of heteronuclear rare-earth interactions is imaginative. It appears that polyoxometallolanthanoates are ideal for this type of investigation. Three structural types of Tb3+/Eu3+ heterolanthanide-multinuclear polyoxometalates, K15H3[Tb1.4Eu1.6(H2O)3(SbW9O33)(W5O18)3]•25.5H2O, Na7H19[Tb4.3Eu1.7O2(OH)6(H2O)6Al2(Nb6O19)5]•47H2O, and [NH4]12H2[Tb3.1Eu0.9(MoO4)(H2O)16(Mo7O24)4]•13H2O are studied by crystal structures, emission and excitation spectra, and emission decay dynamics. The excitation of the Tb3+ 7F6→5D4 transitions produces not only the emission lines of Tb3+, but also those of Eu3+, accompanied by nonexponential rise and decay curves of the emission from Tb3+ and Eu3+. There is no significant exchange interaction between the lanthanide ions, as a result of the coordination of aqua and/or hydroxo ligands to the lanthanide ions. The mechanism of the Tb3+→Eu3+ energy transfer is identified as a Forster-Dexter-type energy transfer from Tb3+ (donor) to Eu3+ (acceptor). The nearest-neighbor energy-transfer rates by electric dipole-dipole interactions between a Tb-Eu pair at 4.2K are estimated to be 4.5 × 104, 4.7 × 105, and 4.9 x 103 s−1 and the critical radii at 4.2 K are 10.3, 10.0, and 6.17 Å for K15H3[Tb1.4Eu1.6(H2O)3(SbW9O33)(W5O18)3]•25.5H2O (with Tb-Eu separation of 5.05 Å), Na7H19[Tb4.3Eu1.7O2(OH)6(H2O)6Al2(Nb6O19)5]•47H2O (with 3.76 Å separation), and [NH4]12H2[Tb3.1Eu0.9(MoO4)(H2O)16(Mo7O24)4]•13H2O (with 6.17 Å separation), respectively. The low symmetry (C s or C 1 ) of the LnO 8 (Ln=Tb and Eu) coordination polyhedra allows the nonvanishing electric-dipole transition probability for the 7 F J ↔; 5 D 0 (J=0,l) transitions which leads to a faster transfer rate at high temperatures. The photoexcitation of the host lattices (tungstate, niobate, and molybdate) induced the energy transfer from the oxygen-to-metal charge-transfer {O→M(=Nb, Mo, W) lmct} triplet states to Tb 3+ ( 7 F 6 → 5 D 4 ) and Eu 3+ ( 7 F 0,1,2 → 5 D 0,1 ). In the case of [NH 4 ] 12 H 2 [Tb 3.1 Eu 0.9 (MoO 4 )(H 2 O) 16 (Mo 7 O 24 ) 4 ]•13H 2 O this transfer is not complete and the O→Mo lmct triplet emission of molybdates is observed to provide the rate constant for the energy transfer to Tb3+/Eu3+ sites with 4.4 × 106 s−1
Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis (2006)

During interkinesis, a metaphase II (MetII) spindle is built immediately after the completion of meiosis I. Oocytes then remain MetII arrested until fertilization. In mouse, we find that early mitotic inhibitor 2 (Emi2), which is an anaphase-promoting complex inhibitor, is involved in both the establishment and the maintenance of MetII arrest. In MetII oocytes, Emi2 needs to be degraded for oocytes to exit meiosis, and such degradation, as visualized by fluorescent protein tagging, occurred tens of minutes ahead of cyclin B1. Emi2 antisense morpholino knockdown during oocyte maturation did not affect polar body (PB) extrusion. However, in interkinesis the central spindle microtubules from meiosis I persisted for a short time, and a MetII spindle failed to assemble. The chromatin in the oocyte quickly decondensed and a nucleus formed. All of these effects were caused by the essential role of Emi2 in stabilizing cyclin B1 after the first PB extrusion because in Emi2 knockdown oocytes a MetII spindle was recovered by Emi2 rescue or by expression of nondegradable cyclin B1 after meiosis I.
Abstract B22: The evaluation of the synthetic triterpenoid CDDO-ethyl amide and the histone deacetylase inhibitor vorinostat for prevention of pancreatic cancer . (2012)

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the U.S. and is almost always fatal. While prevention offers the most promising approach for reducing the mortality of this disease, there is still a need to develop effective drugs for the prevention and treatment of pancreatic cancer and to test these drugs in relevant animal models. Hingorani et al have developed the autochthonous LSL-KrasG12D/+;LSL-Trp53R127H/+;Pdx-1-Cre (KPC) mouse model of pancreatic cancer. These KPC transgenic mice closely replicate the genetic lesions, clinical symptoms, and histopathology found in human pancreatic cancer. A significant infiltration of immune cells, including tumor-associated macrophages, myeloid-derived suppressor cells and regulatory T cells, has been observed in these mice, and these immune cells appear to drive disease progression. Our recent, unpublished studies suggest that the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid (SAHA)) and synthetic triterpenoids inhibit the production of the inflammatory mediator nitric oxide in RAW macrophage-like cells, suppress the release of chemokines from primary tumor cells, and reduce the infiltration of tumor-associated macrophages in vivo. In order to test these drugs against pancreatic cancer, KPC mice were fed powdered control diet or diet containing the triterpenoid CDDO-Ethyl amide (CDDO-EA; 400 or 600 mg/kg diet), SAHA (250 mg/kg diet) or the combination of CDDO-EA and SAHA (400 and 250 mg/kg diet, respectively). Diets were started beginning at 4 weeks of age and were continued until the mice displayed overt symptoms (cachexia, abdominal distension) of pancreatic cancer. CDDO-EA, SAHA, and the combination (n ~ 25 per group) all significantly (P Supported by the Sidney Kimmel Foundation for Cancer Research, the American Cancer Society, NIH/NCI, and Reata Pharmaceuticals, Inc. Citation Format: Karen Liby, Darlene Royce, Charlotte Williams, Renee Risingsong, Kim Tran. The evaluation of the synthetic triterpenoid CDDO-ethyl amide and the histone deacetylase inhibitor vorinostat for prevention of pancreatic cancer . [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B22.
Novel Anomaly of the Hyperfine Structure in Triplet ESR Spectra and Absolute Sign Determination of the Zero-Field and Hyperfine Splitting Constants (1971)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Machio Iwasaki, Kayoko Minakata, Kazumi Toriyama; Novel Anomaly of the Hyperfine Structure in Triplet ESR Spectra and Absolute Sign Determination of the Zero‐Field and Hyperfine Splitting Constants. J. Chem. Phys. 1 April 1971; 54 (7): 3225–3226. https://doi.org/10.1063/1.1675314 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioThe Journal of Chemical Physics Search Advanced Search |Citation Search
Virtual Special Issue: New Drug Modalities in Medicinal Chemistry, Pharmacology, and Translational Science (2023)

RecommendationsW hen opening a journal focused on medicinal chemistry or drug development from 10, 20, or 50 years ago, one will find familiar themes.One is the steady dominance of enzymes and receptors as targets for agents acting across the antagonist/partial agonist/agonist continuum.In addition, those agents would most likely have classical small, drug-like molecular structures or be derived from a natural product heritage.And although the years have seen advances like the addition of biologics, many important therapeutic goals continue to be addressed by small molecules acting through established pathways.No healthy scientific endeavor stays still, however, and exciting new approaches are being pursued throughout every avenue of drug discovery.In this Virtual Special Issue (VSI), we seek to highlight papers that feature these new modalities and, in so doing, provide a spotlight on the cutting edge of contemporary medicinal chemistry.These papers were mostly submitted through the normal procedure and reflect all article types of the host journals for this VSI.We have sought to be broad-minded in the identification of these papers, although several themes do reveal themselves throughout the portfolio.For example, protein degradation has very quickly become a go-to technique across therapeutic areas, and synthetic molecules, like macrocycles, in addition to oligopeptides, that split the molecular mass difference between classical drugs and the biologics class, are receiving increased attention.Besides classical biologics, i.e., polypeptides, various further polymeric drugs, e.g., aptamers consisting of single-stranded nucleic acids, and polymeric polyphenols (tannic acids), are subjects of publications in this VSI.Several articles focus on conjugates of small molecules to alter pharmacokinetic properties and to modulate pharmacological effects.Finally, multi-target drugs are described, that prove the recent paradigm change from drugs for single targets to polypharmacology.Articles published in this VSI also describe molecules interacting with new drug targets, and with novel mechanisms of action.Across all of these new modalities, the value of mid-size (MW 600-800) and large molecules (MW 900+), so-called beyond rule-of-5 compounds, is clear.These atypical molecules demonstrate excellent physiochemical and DMPK (drug metabolism and pharmacokinetics) properties, affording oral bioavailability and central nervous system penetration.Have we been too restrictive on ourselves, and operating/designing within unnecessary limitations the past 20 years?Only time and new drug applications will tell.We're not time travelers and therefore unable to predict what medicinal chemistry will look like in the future, but if past experience is any guide, these new modalities stand a good chance of being viewed as old standards 20 years from now.
Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation (2000)

Unrelated cord blood (UCB) is being used as a source of alternative hematopoietic stem cells for transplantation with increasing frequency. From November 1994 to February 1999, 30 UCB transplant procedures were performed for both malignant and nonmalignant diseases in 27 children, aged 0.4 to 17.1 years. Patients received either HLA-matched (n = 3) or 1- or 2-antigen–mismatched (n = 27) UCB following 1 of 2 standardized preparative and graft-versus-host disease regimens (hyperfractionated total body irradiation, cyclophosphamide, and antithymocyte globulin [ATG] with cyclosporine A and methotrexate; or busulfan, melphalan, and ATG with cyclosporine A and prednisone). The median time to neutrophil and platelet engraftment was 27 days (12-60 days) and 75 days (33-158 days) posttransplantation, respectively. No correlation was noted between neutrophil and platelet engraftment and nucleated cells per kilogram, CD34+ cells per kilogram infused, or cytomegalovirus status of recipient. The cumulative probability of acute grade 2 or greater graft-versus-host disease (GVHD) was 37.2%, and of grade 3 or greater GVHD was 8.8%. No patients developed chronic GVHD. CD4, CD19, and natural killer cell recovery was achieved at a median of 12, 6, and 2 months, respectively. CD8 recovery was delayed at a median of 9 months. Normal mitogen response was achieved at 6 to 9 months. The probability of survival, disease-free survival, and event-free survival at 1 year was 52.3% (34.1%-70.5%), 54.7% (34.5%-74.9%) and 49.6% (29.9%-69.4%), respectively. This series of 30 UCB transplants suggests that although CD8 cell recovery is delayed, the pattern of immune reconstitution with UCB is similar to that reported for other stem cell sources.
Expansions and contractions of the FMR1 CGG repeat in 5,508 transmissions of normal, intermediate, and premutation alleles (2019)

Instability of the FMR1 repeat, commonly observed in transmissions of premutation alleles (55-200 repeats), is influenced by the size of the repeat, its internal structure and the sex of the transmitting parent. We assessed these three factors in unstable transmissions of 14/3,335 normal (~5 to 44 repeats), 54/293 intermediate (45-54 repeats), and 1561/1,880 premutation alleles. While most unstable transmissions led to expansions, contractions to smaller repeats were observed in all size classes. For normal alleles, instability was more frequent in paternal transmissions and in alleles with long 3' uninterrupted repeat lengths. For premutation alleles, contractions also occurred more often in paternal than maternal transmissions and the frequency of paternal contractions increased linearly with repeat size. All paternal premutation allele contractions were transmitted as premutation alleles, but maternal premutation allele contractions were transmitted as premutation, intermediate, or normal alleles. The eight losses of AGG interruptions in the FMR1 repeat occurred exclusively in contractions of maternal premutation alleles. We propose a refined model of FMR1 repeat progression from normal to premutation size and suggest that most normal alleles without AGG interruptions are derived from contractions of maternal premutation alleles.
Tunable optical add-drop multiplexer based on silicon photonic wire waveguides (2006)

A wavelength tunable optical add-drop multiplexer based on silicon photonic wire waveguides with Bragg-grating-reflectors was demonstrated by tuning the dropping wavelength through thermooptic effect. A 6.6-nm dropping wavelength shift was obtained at a 0.82-W heating power. For the device that is presently polarization-dependent, the 3-dB channel-dropping bandwidth was 0.4 nm and the extinction ratio at the dropping wavelength for port THROUGH was better than 17 dB for assuming 1.6-nm wavelength spacing dense wavelength-division multiplexing. The average tuning speed was about 200 /spl mu/s.
Analysis of synchronous reluctance machine with magnetically coupled three-phase windings and reactive power compensation (2010)

Synchronous reluctance machine with simple salient rotor is known to have poor power factor because of its poor reactance ratio. This study presents the use of an auxiliary winding attached to a balanced capacitor to improve the effective reactance ratio as well as the performance characteristics of synchronous reluctance machine. A unique feature of this configuration is that although the machine runs at synchronous speed, the effective reactance ratio of the machine can be improved by appropriate sizing of the capacitor attached to the auxiliary winding, with the constraint of the ampere turn rating of the auxiliary winding. The operational characteristics of a simple salient rotor synchronous reluctance machine equipped with this configuration were investigated and shown to have a desirable performance. How the effective reactance ratio, power factor and airgap flux distribution depend on the size of capacitor attached to the auxiliary winding is determined using a simplified mathematical model of the system. Analytical results and experimental measurements are in good agreement, and demonstrate the effectiveness and benefits of the configuration.
Synthesis of 2-Acyltetrahydroisoquinolines and 2-Acyl-1,2,3,4-tetrahydro-1,2-benzothiazine-1,1-diones by Electrophilic Substitution Reactions of N-Acyl-2-Phenylethylamines (1998)

Abstract 1-Substituted- 5, 1,5-substituted 7,8-dioxygenated-2-acyltetrahydroisoquino-lines 10 and 2-acyl-1,2,3,4-tetrahydro-1,2-benzothiazine-1,1-diones 12 has been obtained by the reaction of N-acyl-2-phenylethylamines with aldehydes or chlorosulfonic acid as a result of an electrophilic hydroxyalkylation and chlorosulfonation of the aromatic ring.
Isolation and Characterization of a Diverse Set of Genes from Carrot Somatic Embryos (1996)

The early events in plant embryogenesis are critical for pattern formation, since it is during this process that the primary apical meristems and the embryo polarity axis are established. However, little is known about the molecular events that are unique to the early stages of embryogenesis. This study of gene expression during plant embryogenesis is focused on identifying molecular markers from carrot (Daucus carota) somatic embryos and characterizing the expression and regulation of these genes through embryo development. A cDNA library, prepared from polysomal mRNA of globular embryos, was screened using a subtracted probe; 49 clones were isolated and preliminarily characterized. Sequence analysis revealed a large set of genes, including many new genes, that are expressed in a variety of patterns during embryogenesis and may be regulated by different molecular mechanisms. To our knowledge, this group of clones represents the largest collection of embryo-enhanced genes isolated thus far, and demonstrates the utility of the subtracted-probe approach to the somatic embryo system. It is anticipated that many of these genes may serve as useful molecular markers for early embryo development.
Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2(V617F) in mice. - eScholarship (2012)

STAT5 proteins are constitutively activated in malignant cells from many patients with leukemia, including the myeloproliferative neoplasms (MPNs) chronic myeloid leukemia (CML) and polycythemia vera (PV), but whether STAT5 is essential for the pathogenesis of these diseases is not known. In the present study, we used mice with a conditional null mutation in the Stat5a/b gene locus to determine the requirement for STAT5 in MPNs induced by BCR-ABL1 and JAK2(V617F) in retroviral transplantation models of CML and PV. Loss of one Stat5a/b allele resulted in a decrease in BCR-ABL1-induced CML-like MPN and the appearance of B-cell acute lymphoblastic leukemia, whereas complete deletion of Stat5a/b prevented the development of leukemia in primary recipients. However, BCR-ABL1 was expressed and active in Stat5-null leukemic stem cells, and Stat5 deletion did not prevent progression to lymphoid blast crisis or abolish established B-cell acute lymphoblastic leukemia. JAK2(V617F) failed to induce polycythemia in recipients after deletion of Stat5a/b, although the loss of STAT5 did not prevent the development of myelofibrosis. These results demonstrate that STAT5a/b is essential for the induction of CML-like leukemia by BCR-ABL1 and of polycythemia by JAK2(V617F), and validate STAT5a/b and the genes they regulate as targets for therapy in these MPNs.
Comparison between ruthenium-based and other ohmic contact systems to p-type GaAs (1992)

A conventional furnace annealed Ru/Au ohmic contact system on p-GaAs has been investigated. Electrical and morphological characteristics of this contact system were compared with other systems such as Cr/Au, Ti/Pt, and Mn/Au. The Ru/Au contact system has been shown to have superior surface morphology and a comparable specific contact resistance value, even after annealing at 485 °C. The advantages of utilizing Ru as contact material to GaAs are that it forms high quality, thermally stable Schottky contacts to n-GaAs and thermally stable ohmic contacts with low specific contact resistance to p-GaAs. This dual nature of Ru contacts to GaAs makes them extremely important for future use in devices such as heterojunction bipolar transistors (HBTs) and solid state lasers.
Web Tracking Technologies and Protection Mechanisms (2017)

Billions of users browse the Web on a daily basis, leaving their digital traces on millions of websites. Every such visit, every mouse move or button click may trigger a wide variety of hidden data exchanges across multiple tracking companies. As a result, these companies collect a vast amount of user's data, preferences and habits, that are extremely useful for online advertisers and profitable for data brokers, however very worrisome for the privacy of the users. In this \emph{3-hours tutorial} we will cover the vide variety of Web tracking technologies, ranging from simple cookies to advanced cross-device fingerprinting. We will describe the main mechanisms behind web tracking and what users can do to protect themselves. Moreover, we will discuss solutions Web developers can use to automatically eliminate tracking from the third-party content they include in their applications. This tutorial will be of interest to a \emph{general audience} of computer scientists, and \emph{we do not require any specific prerequisite knowledge} for attendees. We will cover the following tracking mechanisms: \begin{itemize} \item third-party cookie tracking, and other stateful tracking techniques that enables tracking across multiple websites, \item cookie respawning that is used to re-create deleted user cookies, \item cookie synching that allows trackers and ad agencies to synchronise user IDs across different companies, \item browser fingerprinting, including Canvas, WebRTC and AudioContext fingerprinting \item cross-browser device fingerprinting, allowing trackers to recognise users across several devices. \end{itemize} We will then demonstrate prevalence of such techniques on the Web, based on previous research. We will present the advertisement ecosystem and explain how Web technologies are used in advertisement, in particular in Real-Time-Bidding (RTB). We will explain how cookie synching is used in RTB and present recent analysis on how much a user's tracking data is worth. We will discuss the mechanisms the website owners use to automatically interact with the ad agencies, and explain its consequences on user's security and privacy. To help users protect themselves from Web tracking, we will give an overview of existing solutions. We'll start with the browser settings, and show that basic third-party cookie tracking is still possible even in the private browser mode of most common Web browsers. We then present privacy-protecting browser extensions and compare how efficient they are in protection from Web tracking. Then, we'll present possible protection mechanisms based on browser randomisation to protect from advanced fingerprinting techniques. Finally, we will present solutions for Web developers, who want to include third-party content in their websites, but would like to automatically remove any tracking of their users. In particular, we will discuss simple solutions that exist today for social plugins integration, and propose more advanced server-side based solutions that are a result of our own research.