gebhart/patrepeval huggingface dataset:
The farnesyltransferase inhibitor Zarnestra synergizes with paclitaxel to induce mitotic arrest and apoptosis in multiple myeloma cells (2004)

3865 Despite significant recent advances in the treatment of multiple myeloma (MM), it remains an incurable disease with a median survival of 3 to 6 years. Recently, we conducted a phase II clinical trial with the farnesyltransferase inhibitor Zarnestra in patients with relapsed MM and demonstrated that Zarnestra as a single agent induces disease stabilization in about 50% of the patients. In the present study, Zarnestra was found to synergyze with paclitaxel (taxol) to induce mitotic arrest and apoptosis in 8226 MM cells. Zarnestra synergized with taxol to inhibit proliferation (MTT analysis), to induce apoptosis (TUNEL assay and Cyt. C release) and to cause G2/M arrest (flow cytometric analysis). Taxol also synergyzed with a PI-3K, but not a Mek, inhibitor. Neither taxol nor Zarnestra affected P-Erk levels, but both decreased P-AKT levels. VEGF levels in the cells as well as in the culture medium decreased only when both Zarnestra and taxol were used with or without IL-6 stimulation. The combination of Zarnestra and taxol also blocked the stimulation of Bcl-XL expression by IL-6. Finally, taxol was shown to enhance the antitumor activity of Zarnestra in vivo with the 8226 myeloma SCID-hu mouse model. Our results provide the basis to evaluate combination therapy of Zarnestra and taxol in myeloma patients.
D-xylo and Lyxofuranonucleosides Reviewed: Some Suggestions on The Mechanism of Activity of Antiviral Nucleosides (1985)

Abstract D-Xylo and Lyxofuranonucleosides have not been extensively studied. Therefore in order to perform a systematic Structure-Antiviral Activity Relationship of the nucleoside analogs we have first synthesized their α and β anomers, some of them being unknown or their structure doubtful in the literature.
Imaging Cellular Distribution of Bcl Inhibitors Using Small Molecule Drug Conjugates (2014)

Overexpression of anti-apoptotic proteins such as Bcl-2 is a cellular mechanism to evade apoptosis; consequently, Bcl-2 inhibitors are being developed as anticancer agents. In this work, we have synthesized a fluorescent version of ABT-199 in an effort to visualize a drug surrogate by high resolution imaging. We show that this fluorescent conjugate has comparable Bcl-2 binding efficacy and cell line potency to the parent compound and can be used as an imaging agent in several cancer cell types. We anticipate that this agent will be a valuable tool for studying the single-cell distribution and pharmacokinetics of ABT-199 as well the broader group of BH3-mimetics.
Perlecan and the Blood-Brain Barrier: Beneficial Proteolysis? (2012)

The cerebral microvasculature is important for maintaining brain homeostasis. This is achieved via the blood-brain barrier (BBB), composed of endothelial cells with specialized tight junctions, astrocytes, and a basement membrane (BM). Prominent components of the BM extracellular matrix (ECM) include fibronectin, laminin, collagen IV, and perlecan, all of which regulate cellular processes via signal transduction through various cell membrane bound ECM receptors. Expression and proteolysis of these ECM components can be rapidly altered during pathological states of the central nervous system. In particular, proteolysis of perlecan, a heparan sulfate proteoglycan, occurs within hours following ischemia induced by experimental stroke. Proteolysis of ECM components following stroke results in the degradation of the BM and further disruption of the BBB. While it is clear that such proteolysis has negative consequences for the BBB, we propose that it also may lead to generation of ECM protein fragments, including the C-terminal domain V (DV) of perlecan, that potentially have a positive influence on other aspects of CNS health. Indeed, perlecan DV has been shown to be persistently generated after stroke and beneficial as a neuroprotective molecule and promoter of post-stroke brain repair. This mini-review will discuss beneficial roles of perlecan protein fragment generation within the brain during stroke.
Realization of the field-free Josephson Diode (2021)

The superconducting analog to the semiconducting diode, the Josephson diode, has long been sought, with multiple avenues to realization proposed by theorists. Exhibiting magnetic-field free, single directional superconductivity with Josephson coupling of the supercurrent across a tunnel barrier, it would serve as the building-block for next-generation superconducting circuit technology. Here we realized the field-free Josephson diode using an inversion symmetry breaking heterostructure of $\mathrm{NbSe_2/Nb_3Br_8/NbSe_2}$. We demonstrate, for the first time without magnetic field, the junction can be superconducting in one direction while normal in the opposite direction. Based on that, half-wave rectification of a square-wave excitation was achieved with low switching current density ($~2.2\times 10^2 \mathrm{A/cm^2}$), high rectification ratio ($~10^4$) and high robustness (at least $10^4$ cycles). We also demonstrate symmetric $ΔI_\mathrm{c}$ (the difference between positive and negative critical currents) behavior with field and the expected Fraunhofer current phase relation of a Josephson junction. This realization raises fundamental questions about the Josephson effect through an insulator when breaking symmetry, and opens the door to ultralow power, high speed, superconducting circuits for logic and signal modulation.
Three- and four-photon absorption in InAs (1996)

In a series of experiments using 125 ps CO2 laser pulses, the authors identified conditions for three- and four-photon absorption in 1-mm samples of bulk InAs (N approx. 5 × 1016 cm-3). Three-photon absorption (3PA) is studied at a fixed laser wavelength of 9.54 μm. At room temperature, 3ℏω > Eg = 0.36 eV. At 15 K, however, 3 ℏω < Eg = 0.42 eV and 3PA cannot occur. A sequence of open aperture Z scans were performed, varying only sample temperature.
Shear Patterning of Microdominos: A New Class of Procedures for Making Micro‐ and Nanostructures (2004)

Mit einfachen Mitteln werden komplexe, regelmäßig angeordnete 3D-Mikrostrukturen erzeugt, die mit anderen Methoden nur schwer oder überhaupt nicht zugänglich sind (siehe Bild). Das Besondere an der neuen Technik ist die Nutzung von Scherkräften. Als Anwendungsbeispiel ist die Erzeugung von nanoskaligen flachen Mustern beschrieben.
FIP1L1/PDGFRA is a molecular marker of chronic eosinophilic leukaemia but not for systemic mastocytosis (2007)

Peer Reviewed
Three Genes of the Arabidopsis RPP1 Complex Resistance Locus Recognize Distinct Peronospora parasitica Avirulence Determinants (1998)

Miguel A. Botella, Jane E. Parker, Louise N. Frost, Peter D. Bittner-Eddy, Jim L. Beynon, Michael J. Daniels, Eric B. Holub, Jonathan D. G. Jones, Three Genes of the Arabidopsis RPP1 Complex Resistance Locus Recognize Distinct Peronospora parasitica Avirulence Determinants, The Plant Cell, Vol. 10, No. 11 (Nov., 1998), pp. 1847-1860
Presenilin-1 is associated with Alzheimer's disease amyloid. (1997)

Mutations in presenilin (PS)-1 and -2, located on chromosome 14 and 1 respectively, are the major association with early-onset familial Alzheimer's disease (FAD). FAD has also been linked to mutations in the amyloid beta precursor protein (beta PP), and the presence of the apolipoprotein E4 allele is a risk factor for late-onset AD. The role of PS in FAD and in sporadic AD is unclear. We previously reported the presence of a PS-1 carboxyl-terminal epitope in neuritic plaques (Wisniewski T, Palha JA, Ghiso J, Frangione B: S182 protein in Alzheimer's disease neuritic plaques. Lancet 1995, 346:1366). In the present study, we examined a number of biochemically different cerebral and systemic amyloidoses, finding the PS-1 carboxy epitope only in association with amyloid beta (A beta) lesions. We confirm the presence of this epitope ultrastructurally in neuritic plaques. In addition, biochemical and amino acid sequence data are presented for an association of the 18-kd carboxy fragment of PS-1 with neuritic plaques with a start at residue 300. Three of the proteins with linkage to AD have now been found as components of neuritic plaques. It remains to be determined whether all of these proteins are involved in the same or different pathological pathway(s) and which of these proteins is the most important for the common, late-onset form of AD.
Novel and Potent 3‐(2,3‐Dichlorophenyl)‐4‐(benzyl)‐4H‐1,2,4‐triazole P2X7 Antagonists. (2007)

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, please click on HTML or PDF.
An Effective Way to Large-Scale Robot-Path-Planning Using a Hybrid Approach of Pre-Clustering and Greedy Heuristic (2020)

Robot-path-planning seeks the shortest path to optimize the motion cost for robots. In robot-path-planning, the computational time will significantly increase if the moving targets rise largely, also known as the large-scale TSP. Hence, the current algorithms for the shortest path planning may be ineffective in the large-scale TSP. Aimed at the real-time applications that a robot must achieve as many goals as possible within limited time and the computational time of a robot has to be short enough to provide the next moving signal in time. Otherwise, the robot will be trapped into the idle status. This work proposes a hybrid approach, called the pre-clustering greedy heuristic, to tackle the reduction of computational time cost and achieve the near-optimal solutions. The proposed algorithm demonstrates how to lower the computational time cost drastically via smaller data of a sub-group, divided by k-means clustering, and the intra-cluster path planning. An algorithm is also developed to construct the nearest connections between any two unconnected clusters, ensuring the inter-cluster tour is the shortest. As a result, by utilizing the proposed heuristic, the computational time is significantly reduced and the path length is more efficient than the benchmark algorithms, while the input data grow up to a large scale. In applications, the proposed work can be applied practically to the path planning with large-scale moving targets, for example, the employment for the ball-collecting robot in a court.
Microstructure and Mechanical Performance of Cold Metal Transfer Spot Joints of AA6061-T6 to Galvanized DP590 Using Edge Plug Welding Mode (2015)

Dissimilar joining of aluminum to steel poses a challenge for arc welding. In this study, aluminum AA6061-T6 and hot dipped galvanized DP590 steel were joined using the Fronius cold metal transfer (CMT) welding process applying an edge plug welding mode (EPW). The correlation of the welding parameters, weld characteristics, and weld strength was systematically investigated. It was found that the EPW mode created a zinc-rich zone at the weld root along the Al–steel faying interface which transitioned to a continuous and compact intermetallic compounds (IMC) layer in the middle portion of the joint. The fracture propagation in lap-shear specimens was affected by this increase of IMC layer thickness. At a wire feed speed (wfs) of 5.6 m/min, the fracture initiated along the zinc-rich layer at the faying interface and then, upon meeting the compact IMC layer, propagated into the aluminum weld nugget. Propagation followed a path within the weld nugget along the boundary between columnar and equiaxed grains leading to weld nugget pullout upon fracture. For IMC layer peak thicknesses below 10 μm, the strength increased as a function of weld nugget diameter. However, larger heat inputs resulted in IMC layer thicknesses greater than 10 μm and interfacial fracture.
CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice (2014)

Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress than wild-type control mice. These effects were associated with inhibition of NF-κB/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced inflammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-κB/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant effects that could aid in the design of new therapies for the prevention and treatment of NAFLD.
Optical computed tomography in a turbid medium using early arriving photons (2000)

We employ photon migration to image absorbing objects embedded in a turbid medium. For improved resolution, we use early arriving photons (a few hundred picoseconds in excess of the time of flight), a regime in which the diffusion approximation breaks down. Our image reconstruction method is based on extension of x-ray computed tomography (CT) to the optical regime. The CT algorithm must be generalized to take into account the distributions of photon paths. We express the point spread function (PSF) in terms of the Green's function for the transport equation. This PSF then provides weighting functions for use in a generalized series expansion method of x-ray CT. Experiments were performed on a turbid medium with scattering and absorption properties similar to those of human breast tissue. Multiple absorbers were embedded into the medium to mimic tumors. Coaxial transmission scans were collected in two projections, and the early-time portions were analyzed. Through accurate modeling, we could remove the blurring associated with multiple scattering and obtain high-resolution images. Our results show that the diffusion approximation PSF is inadequate to describe the early arriving photons. A PSF incorporating causality is required to reconstruct accurate images of turbid media.
The DNA methylation locusDDM1 is required for maintenance of gene silencing in Arabidopsis (1998)

To investigate the relationship between cytosine methylation and gene silencing in Arabidopsis, we constructed strains containing the ddm1 hypomethylation mutation and a methylated and silenced PAI2 tryptophan biosynthetic gene (MePAI2) that results in a blue fluorescent plant phenotype. The ddm1 mutation had both an immediate and a progressive effect on PAI gene silencing. In the first generation, homozygous ddm1 MePAI2 plants displayed a weakly fluorescent phenotype, in contrast to the strongly fluorescent phenotype of the DDM1 MePAI2 parent. After two generations of inbreeding by self-pollination, the ddm1/ddm1 lines became nonfluorescent. The progressive loss of fluorescence correlated with a progressive loss of methylation from the PAI2 gene. These results indicate that methylation is necessary for maintenance of PAI gene silencing and that intermediate levels of DNA methylation are associated with intermediate gene silencing. The results also support our earlier hypothesis that ddm1 homozygotes act as "epigenetic mutators" by accumulating heritable changes in DNA methylation that can lead to changes in gene expression.
The integrated LIM-peptidase domain of the CSA1-CHS3/DAR4 paired immune receptor detects changes in DA1 peptidase inhibitors in Arabidopsis (2023)

White blister rust, caused by the oomycete Albugo candida, is a widespread disease of Brassica crops. The Brassica relative Arabidopsis thaliana uses the paired immune receptor complex CSA1-CHS3/DAR4 to resist Albugo infection. The CHS3/DAR4 sensor NLR, which functions together with its partner, the helper NLR CSA1, carries an integrated domain (ID) with homology to DA1 peptidases. Using domain swaps with several DA1 homologs, we show that the LIM-peptidase domain of the family member CHS3/DAR4 functions as an integrated decoy for the family member DAR3, which interacts with and inhibits the peptidase activities of the three closely related peptidases DA1, DAR1, and DAR2. Albugo infection rapidly lowers DAR3 levels and activates DA1 peptidase activity, thereby promoting endoreduplication of host tissues to support pathogen growth. We propose that the paired immune receptor CSA1-CHS3/DAR4 detects the actions of a putative Albugo effector that reduces DAR3 levels, resulting in defense activation.
ChemInform Abstract: Photochemical Disproportionation of Mn2(CO)10. Nineteen‐Electron Intermediates and Ligand and Intensity Dependence. (1986)

Abstract The photochemical disproportionation of (I) proceeds first to (II) and (III).
BCR/ABL Promotes Dendritic Cell–Mediated Natural Killer Cell Activation (2005)

BCR/ABL fusion gene, encoding a paradigmatic tyrosine kinase involved in chronic myelogenous leukemia (CML), can modulate the expression of genes involved in natural killer (NK) cell target recognition. Recent reports outline the role of allogeneic antileukemic NK effectors in the graft-versus-leukemia effect but the regulation of NK cell activation in the setting of graft-versus-leukemia effect remains unknown. Here we show that dendritic cells derived from monocytes of CML patients are selectively endowed with NK cell stimulatory capacity in vitro. We further show, using a gene transfer approach in mouse bone marrow progenitors, that ABL/ABL is necessary to promote dendritic cell-mediated NK cell activation. The dendritic cell/NK cell cross-talk in ABL/ABL-induced CML seems unique because JunB or IFN consensus sequence binding protein loss of functions, associated with other myeloproliferative disorders, do not promote dendritic cell-mediated NK cell activation. NK cell activation by leukemic dendritic cells involves NKG2D activating receptors and is blocked by imatinib mesylate. Indeed, ABL/ABL translocation enhances the expression levels of the NKG2D ligands on dendritic cells, which is counteracted by imatinib mesylate. Altogether, the clonal ABL/ABL dendritic cells display the unique and selective ability to activate NK cells and may participate in the NK cell control of CML. This study also highlights the deleterious role of imatinib mesylate at the dendritic cell level for NK cell activation.
Anticancer Agents from Unique Natural Products Sources (2003)

The National Cooperative Natural Products Drug Discovery Group (NCNPDDG) “Anticancer Agents from Unique Natural Products Sources, CA 67786” was first awarded in September 1995. The goal of the project is to discover and develop novel anticancer agents from a variety of natural products sources. The key accomplishments of this NCDDG which will be highlighted in this manuscript include:Development of tools to probe fungi for the production of novel natural products by DNA-based probes. Discovery that the majority of these fungi can produce natural products via nonribosomal peptide synthetases, polyketide synthases, or both – a much larger percentage than current culturing techniques reveal.Identification of the MDR-selective cytotoxic agent austocystin D, and use of a novel yeast deletion strain approach to help identify its molecular target(s).Identification of hemiasterlin and other naturally occurring analogs as potent antimitotic agents with excellent in vivo activity against human solid tumors in mouse models.Development of a total synthesis of hemiasterlin. The utilization of this methodology to provide the first SAR for the hemiasterlin family of antimitotic agents and to identify the synthetic analog HTI-286, which is being examined in clinical trials as an anticancer agent.To provided technology transfer, educational opportunities and compensation to countries of origin for collection and study of their natural product resources. This NCNPDDG program has provided funding to research programs at the University of the Philippines, The University of the South Pacific in the Fiji Islands, Colombo University in Sri Lanka, the Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Brazil, and the University of Papua New Guinea.
Computational arithmetic geometry : AMS special session, April 29-30, 2006, San Francisco State University, San Francisco, California (2008)

Results of Cohen-Lenstra type for quadratic function fields by J. D. Achter The hardness of computing an eigenform by E. Bach and D. Charles Constructing elliptic curves of prime order by R. Broker and P. Stevenhagen Space-time codes and non-associative division algebras arising from elliptic curves by A. Deajim and D. Grant Points of low height on $\mathbb{P}^1$ over number fields and bounds for torsion in class groups by J. S. Ellenberg Supersingular genus-2 curves over fields of characteristic 3 by E. W. Howe Search techniques for root-unitary polynomials by K. S. Kedlaya Yet more elements in the Shafarevich-Tate group of the Jacobian of a Fermat curve by B. Levitt and W. McCallum Stable reduction of $X_0(81)$ by K. McMurdy Isomorphism types of commutative algebras of finite rank over an algebraically closed field by B. Poonen A short guide to $p$-torsion of abelian varieties in characteristic $p$ by R. Pries.
A Novel Production Route for Nylon‐6:. Aspects of Catalysis and Process Development (2007)

Abstract Summary: A novel production route for nylon‐6 out of 6‐aminocapronitrile has been investigated. Hydrolysis of 6‐aminocapronitrile using a solid porous ZrO 2 catalyst is the key step in this novel route. Nylon‐6 with a number average molecular weight of 10 · 10 3 g · mol −1 can be produced from the hydrolyzed 6‐aminocapronitrile. The reactor set up for the polycondensation can in broad outline be the same as the continuously operated reactor used for the ε ‐caprolactam based production of nylon‐6. For the hydrolysis of 6‐aminocapronitrile a number of parallel batchwise operated loop reactors is recommended. A fixed bed of catalyst particles is part of each recirculation loop. Intraparticle mass transport limitation can be avoided by using catalyst particles made of a shell of active ZrO 2 and a massive inert core. An annual production of 50 · 10 6 kg nylon‐6 demands for 5.3 m 3 zirconia.