gebhart/patrepeval huggingface dataset:
Safety, pharmacokinetics (PK), pharmacodynamics (Pd), and antitumor activity in a phase 1b study evaluating anti-ErbB3 antibody KTN3379 in adults with advanced tumors alone and with targeted therapies. (2016)

2501 Background: KTN3379 is a fully human anti-ErbB3 antibody with YTE half-life extension engineering that uniquely binds domain 3 locking ErbB3 in an inactive configuration. ErbB3 is implicated in tumor growth and treatment resistance. A phase 1b study of KTN3379 alone and in combination was undertaken to evaluate safety, PK, Pd, and efficacy (NCT02014909). Methods: Patients (pts) received KTN3379 alone at 5-20 mg/kg (N=21) or in combination at 15 or 20 mg/kg IV q3w with cetuximab (N=16), erlotinib (N=8), vemurafenib (N=4) or trastuzumab (N=9). Safety monitoring and RECIST-based tumor assessments were conducted. PK was evaluated using a two-compartment pharmacokinetic model. Pd markers included serum ErbB3. Archival tumor was tested for neuregulin (NRG) and ErbB3. Results: 58 total pts were treated. No DLTs occurred in 21 pts receiving KTN3379 alone. DLTs of diarrhea, mucositis and rash were observed in 5 of 37 pts treated with combinations. The most common adverse events across all combinations were diarrhea, fatigue, nausea and rash. KTN3379 at or above 15 mg/kg was tolerated in all combination arms. Linear PK was observed at doses between 10 and 20 mg/kg and exceeded target concentration for antitumor activity. There was a trend toward slower clearance and longer half-life of KTN3379 compared to related compounds, consistent with the engineered YTE. Responses included 1 ongoing confirmed CR with cetuximab in a pt with HNSCC who had progressed on cetuximab alone, and 2 confirmed PRs with vemurafenib in pts with BRAF-mutant NSCLC, one of which previously progressed on dabrafenib (2 of 3 responders were NRG+). Analysis of Pd correlates is in progress and will be presented at ASCO. Conclusions: KTN3379 can be safely combined with standard doses of cetuximab, erlotinib, vemurafenib or trastuzumab at 15 to 20 mg/kg. Efficacy was observed including a CR in a pt with HNSCC with cetuximab and PRs in 2 pts with BRAF-mutant NSCLC in combination with vemurafenib. A phase 2 study of the combination of cetuximab and KTN3379 in HNSCC is planned, in addition to currently ongoing phase 1b studies in SCCHN and BRAF-mutant thyroid cancer. Clinical trial information: NCT02014909.
Survival analysis of presumptive prognostic markers among oligodendrogliomas (2005)

9p21 and TP53 mutational status assisted in developing a stricter subclassification of these tumors with prognostic significance. MGMT levels were decreased in a majority of oligodendrogliomas.
Molecular Recognition and Supramolecular Self-Assembly of a Genetically Engineered Gold Binding Peptide on Au{111} (2009)

The understanding of biomineralization and realization of biology-inspired materials technologies depends on understanding the nature of the chemical and physical interactions between proteins and biominerals or synthetically made inorganic materials. Recently, combinatorial genetic techniques permit the isolation of peptides recognizing specific inorganic materials that are used as molecular building blocks for novel applications. Little is known about the molecular structure of these peptides and the specific recognition mechanisms onto their counterpart inorganic surfaces. Here, we report high-resolution atomic force microscopy (AFM), molecular simulation (MS), and geometrical docking studies that detail the formation of an ordered supramolecular self-assembly of a genetically engineered gold binding peptide, 3rGBP(1) ([MHGKTQATSGTIQS](3)), correlating with the symmetry of the Au{111} surface lattice. Using simulated annealing molecular dynamics (SA/MD) studies based on nuclear magnetic resonance (NMR), we confirmed the intrinsic disorder of 3rGBP(1) and identified putative Au docking sites where surface-exposed side chains align with both the <110> and <211> Miller indices of the Au lattice. Our results provide fundamental insight for an atomistic understanding of peptide/solid interfaces and the intrinsic disorder that is inherent in some of these peptide sequences. Analogous to the well-established atomically controlled thin-film heterostructure formation on semiconductor substrates, the basis of today's microelectronics, the fundamental observations of peptide-solid interactions here may well form the basis of peptide-based hybrid molecular technologies of the future.
Functional characterization of a U5 ribozyme: intracellular suppression of human immunodeficiency virus type 1 expression (1992)

We have designed a ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in U5 (at nucleotide +115). This ribozyme was tested in vitro and was found to give efficient and specific digestion of RNA containing the HIV-1 U5 sequence. When the U5 ribozyme was placed into the HIV-1 genome, virus replication was suppressed in tissue culture. Introduction of this ribozyme into cells by using an amphotropic retrovirus vector significantly reduced expression of U5-containing RNA in cells chronically infected with HIV-1. Naive T cells were cocultivated with packaging cells that produce defective amphotropic retroviruses containing the U5 ribozyme. These lymphocytes were found to be partially protected from HIV-1 infection.
Vulnerability in speaker verification - a study of technical impostor techniques (1999)

The development of natural language spoken dialog systems requires collection and labeling of a large set of user-system interactions (knowledge). Ideally, it should be collected from live traffic in the field, since scripted scenarios in a lab typically result in unnatural phraseology. To achieve this, we introduce an extension of the of Oz, a hidden human agent who oversees the machine side of the interaction in collaboration with the automated dialog manager, unbeknownst to the user. The Wizard can provide a continuum of supervision ranging from explicitly controlling every step to a Wizardoverride mode where the machine operates semi-autonomously and the human overrides only when necessary. All interactions are instrumented and entered directly into a database using a standard interface and SQL. The collected data will typically be analyzed in the laboratory to quantify system performance, and to introduce algorithmic improvements prior to a new set of experiments. Over the course of system development iterations, the nature of the Wizard evolves over a continuum of functions from actual control (in the absence of any system knowledge) to passive observer. The user cannot tell the difference.
A compound sensor for biomechanical analyses of buttock soft tissue in vivo. (2001)

A sensor for in vivo biomechanical characterization of buttock soft tissue has been developed and evaluated. The sensor measures interface pressure, applied force, tilt, and rotation angle of the sensor head, and the thicknesses of multiple soft tissue layers. A composite ultrasonic transducer using a 1-3 ceramic-polymer structure was developed for the sensor. The sensor can identify subcutaneous soft tissue interfaces 5 to 65 mm below the skin surface with a 0.26-mm axial resolution, pressure over the range of 0 to 68 kPa, and force over the range of 0 to 3.6 kg. Our purpose for developing the sensor was to study the biomechanical characteristics of buttock soft tissues. Successful identification of distinguishing characteristics in persons with a susceptibility to pressure ulcers may result in the development of a risk assessment tool based on tissue characterization.
[On the differences of molecular aggregates structure with long wave fluorescence in the photosystems I and II]. (1976)

Galactolipase and protenase action on the low temperature fluorescence spectra of light chloroplast fragments obtained from grana or intergrana thylakoids and grana thylakoids system before and after isolation photosystem I particles have been studied. Identical hydrolytic enzymes action in the two type photosystem I particles have been studied. Identical hydrolytic enzymes action in the two type photosystem I particles were observed. Grana thylakoids system after removing photosystem I particles contained photosystem II in the most purified form. These measurements results confirmed our previous suggestion that the band at 735 nm in the low temperature fluorescence spectra of light and heavy fragments belongs to the different native chlorophyll a aggregates.
New synthetic applications of water-soluble acetate Pd/TPPTS catalyst generated in Situ. evidence for a true Pd(0) species intermediate (1995)

Studies on the sp-sp intermolecular coupling reactions with the palladium water-soluble catalyst prepared in situ from palladium(II) acetate and sulfonated triphenylphosphine P(C6H4-m-SO3Na)(3) (TPPTS) in a homogeneous acetonitrile-water system, without Cu(I) promotor, afford diynes with moderate yields (45-65%). Under the same conditions, the sp(2)-sp coupling of 2-iodophenols or 2-iodoanilines and terminal alkynes followed by intramolecular cyclization gives indolic and furanic products in good yields (60-99%). Under these aqueous conditions, an efficient and short synthesis of eutypine illustrated the synthetic potentiality of the coupling. Furthermore, through a series of kinetic and P-31 NMR experiments, we have demonstrated that a mixture of Pd(OAc)(2) and TPPTS affords spontaneously a palladium(0) complex, through formation of bivalent complex Pd(OAc)(2)-(TPPTS)(2). A detailed mechanism of the reaction has been investigated thoroughly and the pertinent rate constants measured. The resulting palladium(0) complex reacts with phenyl iodide via an oxidative addition. This complex is considerably less reactive than the corresponding complex generated from PPh(3), probably due to steric effects.
(Invited) Novel Selector and 3D RRAM Development for High Density Non-Volatile Memory (2015)

The development of a higher density non-volatile memory with the 3D vertical resistive random access memory (VRRAM) has attracted great interest from the memory industry. However, VRRAM currently faces the challenges in selecting the specific cell due to a large number of leakage paths, and fabrication process difficulties. In order to eliminate the sneak path and reduce the power consumption, we have developed a novel selector, which shows nearly ideal selector performances with &gt;10 7 on/off ratio, 0.2 V holding voltage, 10 pA off-state leakage current, sharp on-switch slope of 7 mV/dec, &lt;10 ns turn on speed, &gt;10 9 endurance, &gt;1.6 MA/cm 2 on current density. To investigate the VRRAM performance, we have developed a process flow to fabricate VRRAM and demonstrated a single level sidewall TaOx based VRRAM device. Beside the novel selector and VRRAM integration investigation, we have also proposed a transistor-based novel VRRAM (TB-RRAM) architecture.
Information seeking in organizations: epistemic contexts and contests (2007)

<br><b>Introduction.</b> Organizations seek and use information to understand and enact their worlds. Information constitutes what the organization 'knows' about its environment and its tasks, and thus creates a basis for action. However, the link between information, knowledge, and action is problematic and not well understood. <br><b>Method.</b> We consider three case studies that highlight different aspects of the interaction between information and knowledge in organizations. The first case compares information seeking and use in the due diligence processes of a government agency and a venture capital firm. The second case surfaces the epistemic properties of information seeking in the preparation of country studies by the staff of a German bank. The third case recollects the experience of large-scale information sharing among copier technicians of a multinational office products company. <br><b>Analysis.</b> These case studies suggest that organizations behave as epistemic communities with distinct epistemic and information cultures that influence how information is sought and utilized, and how beliefs are formed and re-formed. <br><b>Conclusion.</b> . To understand information behaviour in organizations is to understand how organizations are simultaneously information-seeking and belief-forming social systems, where information is shaped by epistemic practices as much as beliefs are the outcomes of information seeking and use.
Differential effects of 16α-hydroxyestrone and 2-methoxyestradiol on cyclin D1 involving the transcription factor ATF-2 in MCF-7 breast cancer cells (2005)

We studied the effects of 2-methoxyestradiol (2-ME2) and 16alpha-hydroxyestrone (16alpha-OHE1), two metabolites of estradiol (E2), on DNA synthesis, cell cycle progression and cyclin D1 protein levels in estrogen receptor-positive MCF-7 cells. E2 and 16alpha-OHE1 stimulated DNA synthesis, and 2-ME2 inhibited the stimulatory effects of these agents. E2 and 16alpha-OHE1 stimulated the progression of cells from G1 to S phase and this effect was attenuated by 2-ME2. Western blot analysis showed that E2 and 16alpha-OHE1 increased cyclin D1 protein level by about fourfold compared with control. 2-ME2 had no significant effect on cyclin D1; however, it prevented the accumulation of cyclin D1 in the presence of E2 and 16alpha-OHE1. Cells transfected with a cyclin D1 reporter gene and treated with E2 or 16alpha-OHE1 showed 7- and 9.5-fold increase respectively in promoter activity compared with control. This activity was significantly inhibited by 2-ME2. Cyclin D1 transactivation was mediated by the cAMP response element (CRE) region, which binds activating transcription factor 2 (ATF-2). DNA affinity assay showed 2.5- and 3.5-fold increases in ATF-2 binding to CRE in the presence of E2 and 16alpha-OHE1 respectively. The binding of ATF-2 was inhibited by the presence of 2-ME2. These results show that 2-ME2 can downregulate cyclin D1 and thereby cell cycle progression by a mechanism involving the disruption of ATF-2 binding to cyclin D1 promoter.
IRAC's Insecticide Mode of Action Classification (2011)

This revised 6-page fact sheet explains the rationale behind the Insecticide Resistance Action Committee's (IRAC) insecticide and acaricide mode of action classification and provides a listing of those insecticide common names with their groupings and primary modes of action for insecticides currently registered in Florida. Written by Frederick M. Fishel and published by the UF Department of Agronomy, April 2011. PI-83/PI121: IRAC's Insecticide Mode of Action Classification (ufl.edu)
Intrinsic phase shift between a spin torque oscillator and an alternating current (2007)

We report on a preferred phase shift Δϕ0 between a spin torque oscillator (STO) and an alternating current (Iac) injected at the intrinsic frequency (fSTO) of the STO. In the in-plane (IP) precession mode the STO adjusts to a state where its resistance (or voltage) lags Iac about a quarter of a wavelength [Δϕ0=(87–94)°]. In the IP mode Δϕ0 increases somewhat with the direct current. As the precession changes into the out-of-plane (OOP) mode, Δϕ0 jumps by about 180°, i.e., the STO resistance now precedes Iac about a quarter of a wavelength (Δϕ0=–86°). At the IP/OOP boundary, the alternating current mixes the two oscillation modes and both periodic and chaotic oscillations are observed. As a consequence of mixing, subharmonic terms appear in the STO signal. The intrinsic Δϕ0 will impact any circuit design based on STO technology and will, e.g., have direct consequences for phase locking in networks of serially connected STOs.
Design and fabrication of microfluidic devices for multiphase mixing and reaction (2002)

Using silicon microfabrication technology, microchemical devices have been constructed for the purpose of conducting heterogeneously catalyzed multiphase reactions. The motivation behind the design, the fabrication approach, and the experimental characterization are presented for two classes of devices. The first design involves multiple parallel channels with integrated filter structures to incorporate standard catalytic materials. These catalysts are in the form of finely divided porous particles in a packed-bed arrangement. The second device involves the incorporation of porous silicon as a catalyst support, in the form of a thin layer covering microstructured channels. These microstructured channels simulate the structure of a packed bed and enhance mass transfer relative to an open channel. The ability to incorporate features at the tens-of-microns scale can reduce the mass-transfer limitations by promoting mixing and dispersion for the multiple phases. Directly integrating the catalyst support structures into the channels of the microreactor allows the precise definition of the bed properties, including the support's size, shape and arrangement, and the void fraction. Such a design would find broad applicability in enhancing the transport and active surface area for sensing, chemical, and biochemical conversion devices. Reaction rates for the gas-liquid-solid hydrogenation of cyclohexene using the integrated catalyst with porous silicon as a support compare favorably to those rates obtained with the packed-bed approach. In both cases, the mass transfer coefficient is at least 100 times better than conventional laboratory reactors.
Concomitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Long-term results of the radiation therapy oncology group study 81-17 (1990)

One hundred twenty-four eligible patients with advanced mucosal squamous cell carcinoma of the head and neck were entered into a pilot study of concomitant cisplatin (100 mg/m2 given every 3 weeks for three doses) and standard irradiation. The initial complete response (CR) was 71% with an additional two cases salvaged by surgery for an overall 73% CR. When no keratin was identified in the histologic specimen (41 patients) the CR was 90%. The nasopharynx showed the best CR (89%) among the sites. At 4 years after treatment, the estimated locoregional tumor control rate was 43% and the survival, 34%. When no keratin was present in the specimen, the estimated locoregional control of tumor was superior (56% versus 38% with keratin identified, P = 0.02) and the estimated survival was also superior (48% versus 26%, P = 0.008). Acute treatment-related toxicities included one death due to renal damage and two patients with life-threatening renal damage. The delivery of radiotherapy was not altered. Late toxicity included necrosis -3%, fibrosis -4%, and one fistula. The results of this study justify a randomized trial for the comparison of this combination of cisplatin and radiotherapy versus radiotherapy alone in advanced mucosal carcinomas of the head and neck.
Mechanized Silica Nanoparticles: A New Frontier in Theranostic Nanomedicine (2011)

Medicine can benefit significantly from advances in nanotechnology because nanoscale assemblies promise to improve on previously established therapeutic and diagnostic regimes. Over the past decade, the use of delivery platforms has attracted attention as researchers shift their focus toward new ways to deliver therapeutic and/or diagnostic agents and away from the development of new drug candidates. Metaphorically, the use of delivery platforms in medicine can be viewed as the "bow-and-arrow" approach, where the drugs are the arrows and the delivery vehicles are the bows. Even if one possesses the best arrows that money can buy, they will not be useful if one does not have the appropriate bow to deliver the arrows to their intended location. Currently, many strategies exist for the delivery of bioactive agents within living tissue. Polymers, dendrimers, micelles, vesicles, and nanoparticles have all been investigated for their use as possible delivery vehicles. With the growth of nanomedicine, one can envisage the possibility of fabricating a theranostic vector that could release powerful therapeutics and diagnostic markers simultaneously and selectively to diseased tissue. In our design of more robust theranostic delivery systems, we have focused our attention on using mesoporous silica nanoparticles (SNPs). The payload "cargo" molecules can be stored within this robust domain, which is stable to a wide range of chemical conditions. This stability allows SNPs to be functionalized with stimulus-responsive mechanically interlocked molecules (MIMs) in the shape of bistable rotaxanes and psuedorotaxanes to yield mechanized silica nanoparticles (MSNPs). In this Account, we chronicle the evolution of various MSNPs, which came about as a result of our decade-long collaboration, and discuss advances in the synthesis of novel hybrid SNPs and the various MIMs which have been attached to their surfaces. These MIMs can be designed in such a way that they either change shape or shed off some of their parts in response to a specific stimulus, such as changes in redox potential, alterations in pH, irradiation with light, or the application of an oscillating magnetic field, allowing a theranostic payload to be released from the nanopores to a precise location at the appropiate time. We have also shown that these integrated systems can operate not only within cells, but also in live animals in response to pre-existing biological triggers. Recognizing that the theranostics of the future could offer a fresh approach to the treatment of degenerative diseases including cancer, we aim to start moving out of the chemical domain and into the biological one. Some MSNPs are already being tested in biological systems.
The Visibility Skeleton: A Powerful and Multi-Purpose Global Visibility Tool (1997)

International audience
Inhibition of low‐density lipoprotein oxidation by nitric oxide Potential role in atherogenesis (1993)

The effects of nitric oxide (.NO) and nitrovasodilators on the oxidation of low-density lipoprotein (LDL) have been studied. S-Nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) inhibited Cu(2+)- and 2,2'-azobis-2-amidinopropane hydrochloride-dependent oxidation of LDL as monitored by oxygen consumption and the formation of thiobarbituric acid-reactive substances, conjugated dienes, and lipid hydroperoxides. In the case of SNP, inhibition of LDL oxidation occurred only when the incubation mixture was irradiated with visible light. SNAP, however, exerted a dose-dependent inhibition of Cu(2+)-catalyzed oxidation of LDL even in the dark. Addition of .NO dissolved in deoxygenated buffer also inhibited the progression of LDL oxidation. Mouse peritoneal macrophages were less able to degrade LDL that had been oxidized in the presence of SNAP. Using an .NO electrode, it was estimated that a continuous production of .NO (< or = 760 nM/min) could retard the progression of LDL oxidation. We propose that .NO can inhibit LDL oxidation by acting as a chain-breaking antioxidant that is capable of scavenging carbon-centered and peroxyl radicals. Biological implications of this novel .NO antioxidant property are discussed in relation to atherogenesis and contrasted to the prooxidant property of .NO when generated in the presence of superoxide.