gebhart/patrepeval huggingface dataset:
Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90 (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4733 

Hsp90 is a chaperone protein that allows cancer cells to tolerate the many components of dysregulated pathways. Its inactivation may result in targeting multiple molecular alterations and thus, in reverting the transformed phenotype. The PU-class, a purine-scaffold Hsp90 inhibitor series designed by our laboratory has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of this class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. The study identifies water soluble derivatives (> 5 mM in PBS pH 7.4) of nanomolar potency (IC50 ∼ 50 nM) in cellular and animal models of cancer. Binding affinities of these compounds for Hsp90 correlate well with their biological activities. When administered in vivo to mice bearing MDA-MB-468 human breast cancer xenografted tumors, these agents result in pharmacologically relevant concentrations and accordingly, in modulation of Hsp90-client proteins in tumors.
Effects of Deregulation of Methionine Biosynthesis on Methionine Excretion in <i>Escherichia coli</i> (2005)

Several regulators of methionine biosynthesis have been reported in Escherichia coli, which might represent barriers to the production of excess l-methionine (Met). In order to examine the effects of these factors on Met biosynthesis and metabolism, deletion mutations of the methionine repressor (metJ) and threonine biosynthetic (thrBC) genes were introduced into the W3110 wild-type strain of E. coli. Mutations of the metK gene encoding S-adenosylmethionine synthetase, which is involved in Met metabolism, were detected in 12 norleucine-resistant mutants. Three of the mutations in the metK structural gene were then introduced into metJ and thrBC double-mutant strains; one of the resultant strains was found to accumulate 0.13 g/liter Met. Mutations of the metA gene encoding homoserine succinyltransferase were detected in alpha-methylmethionine-resistant mutants, and these mutations were found to encode feedback-resistant enzymes in a 14C-labeled homoserine assay. Three metA mutations were introduced, using expression plasmids, into an E. coli strain that was shown to accumulate 0.24 g/liter Met. Combining mutations that affect the deregulation of Met biosynthesis and metabolism is therefore an effective approach for the production of Met-excreting strains.
Preamble-based channel estimation techniques for OFDM/OQAM over the powerline (2007)

OFDM/OQAM is a special type of multi-carrier modulation that can be considered as an alternative to conventional OFDM with cyclic prefix (CP) for transmission over multi-path fading channels. Indeed, as it requires no guard interval, it has the advantage of a theoretical higher spectral efficiency. Furthermore, if the pulse shape is well-localized in frequency, the resulting OFDM/OQAM signal satisfies stringent spectrum requirements. However, the classical channel estimation methods used for OFDM cannot be directly applied to OFDM/OQAM. In this paper we present an analysis of this problem and we describe a method for perfect channel estimation in OFDM/OQAM. Then we introduce two new realistic preamble-based channel estimation methods. The performance results are obtained by considering the transmission of an OFDM/OQAM signal over a multi-path power line communication (PLC) channel model. The proposed channel estimation methods are compared to the ones obtained with CP-OFDM.
Erosion Measurements in Linear, Oscillatory, and Combined Oscillatory and Linear Flow Regimes (2004)

Many contaminated sediments and dredged material mixtures of cohesive and non-cohesive sediments occur in wave-dominated environments. In-situ analysis is imperative in understanding the erosion and transport of these sediments. Recent research efforts have developed a flume with unidirectional flow that can measure in-situ sediment erosion with depth (SEDflume). However, the flow regime for the SEDflume has limited applicability to wave-dominated environments. Therefore, a unique device, called the SEAWOLF flume, was developed and used by Sandia National Laboratories to simulate high-shear stress erosion processes experienced in coastal waters where wave forcing dominates the system. The SEAWOLF is capable of testing in-situ or laboratory prepared cores. Erosion rates of cohesive and non-cohesive sediments prepared in the laboratory were determined in oscillatory and combined oscillatory and linear flow regimes. Results of these tests were compared to results from the unidirectional SEDflume. Although maximum shear stresses for oscillatory flows were as high as 7 Pa for the tests, the associated erosion rate for specific sediment over the entire wave cycle were comparable to much lower shear stresses found for constant, linear flows. For example, sediment exposed to a maximum of 7 Pa over a 15 s period resulted in erosion rates similar to results for a constant linear shear stress of 3.4 Pa. Analysis of results for all sediments tested led to a determination of values for an effective shear stress that relates wave-induced erosion to linear flow induced erosion.
Optimal Hour-Ahead Bidding in the Real-Time Electricity Market with Battery Storage Using Approximate Dynamic Programming (2015)

There is growing interest in the use of grid-level storage to smooth variations in supply that are likely to arise with an increased use of wind and solar energy. Energy arbitrage, the process of buying, storing, and selling electricity to exploit variations in electricity spot prices, is becoming an important way of paying for expensive investments into grid-level storage. Independent system operators such as the New York Independent System Operator (NYISO) require that battery storage operators place bids into an hour-ahead market (although settlements may occur in increments as small as five minutes, which is considered near “real-time”). The operator has to place these bids without knowing the energy level in the battery at the beginning of the hour and simultaneously accounting for the value of leftover energy at the end of the hour. The problem is formulated as a dynamic program. We describe and employ a convergent approximate dynamic programming (ADP) algorithm that exploits monotonicity of the value function to find a revenue-generating bidding policy; using optimal benchmarks, we empirically show the computational benefits of the algorithm. Furthermore, we propose a distribution-free variant of the ADP algorithm that does not require any knowledge of the distribution of the price process (and makes no assumptions regarding a specific real-time price model). We demonstrate that a policy trained on historical real-time price data from the NYISO using this distribution-free approach is indeed effective.
Properties of responsive liquid crystal/polymer fibers (2009)

The development of optically responsive liquid crystal (LC)/polymer composite fibers is presented. The morphology and electro-optical properties of LC/polymer fibers are studied with scanning electron microscopy and polarizing optical microscopy, respectively.
EXTH-76. OPTIMIZING TRANSDUCER ARRAY CONFIGURATION FOR TREATING TUMORS IN THE INFRATENTORIAL AND SUPRATENTORIAL BRAIN USING TUMOR TREATING FIELDS (TTFIELDS) (2017)

TTFields is an antimitotic cancer treatment that utilizes low intensity (1–3 V/cm) alternating electric fields in the intermediate frequency (100–300 kHz). TTFields are delivered in two orthogonal directions using 2 pairs of transducer arrays placed on the patient’s scalp. TTFields are approved for Glioblastoma Multiforme (GBM) located in the supratentorial regions of the brain. Infratentorial location of the tumor is rare in adult patients but common in the pediatric population. Infratentorial GBM presents with limited surgical treatment options and a poorer prognosis. Computational studies have shown a strong connection between the array layout and the field distribution within the supratentorial region. Here we present a computer simulations-based study designed to identify new array layouts that could deliver high field intensities concurrently to the supratentorial and infratentorial regions of the brain. To simulate delivery of TTFields to the brain, we used realistic computerized models of an adult human female and an adult male. We simulated various layouts involving placement of the arrays on the scalp and upper neck of the model. All tested layouts delivered field intensities with median intensities above the therapeutic threshold of 1 V/cm to both the infratentorial and supra-tentorial brain. The highest field intensities were delivered to the infratentorial region by a layout, in which each array of one pair was laterally placed superficially to the lower region of the occipital lobe, and the two arrays of the second pair were placed on the calvarium and the superior aspect of the neck. This work shows the feasibility of TTFields in treating tumors in the cerebellum, brain stem and surrounding regions which are located inferior to the tentorium. Careful selection of layouts should enable an effective treatment of multi-focal disease with tumors located in both supratentorial and infratentorial regions simultaneously.
T-V-model: Parameter-based prediction of IPTV quality (2008)

The paper presents a parameter-based model for predicting the perceived quality of transmitted video for IPTV applications. The core model we derived can be applied both to service monitoring and network or service planning. In its current form, the model covers H.264 and MPEG-2 coded video (standard and high definition) transmitted over IP-links. The model includes factors like the coding bit-rate, the packet loss percentage and the type of packet loss handling used by the codec. The paper provides an overview of the model, of its integration into a multimedia model predicting audio-visual quality, and of its application to service monitoring. A performance analysis is presented showing a high correlation with the results of different subjective video quality perception tests. An outlook highlights future model extensions.
BMS-936564/MDX-1338: A Fully Human Anti-CXCR4 Antibody Induces Apoptosis In Vitro and Shows Anti Tumor Activity In Vivo (2011)

Abstract Abstract 1543 BMS-936564/MDX-1338 is a fully human monoclonal antibody that specifically recognizes human CXCR4 and is currently in phase 1 studies in patients with relapsed/refractory acute myeloid leukemia (AML) and multiple myeloma (MM). CXCR4 has been identified as a prognostic indicator for AML and other malignancies, in which greater expression of CXCR4 correlates with disease severity. CXCR4 is a seven-transmembrane, G-protein-coupled receptor in the CXC chemokine receptor family. In response to stimulation by its ligand, the chemokine CXCL12, CXCR4 activates calcium flux, chemotaxis and mediates directional migration of hematopoietic cells. In healthy adults, the receptor is predominantly expressed on B and T cells, monocytes, macrophages, NK and dendritic cells, as well as lymphoid and myeloid precursor cells. Expression of CXCR4 is elevated in a variety of cancers and the interaction of CXCR4 on tumor cells with CXCL12 in the bone marrow promotes tumor cell survival and growth. An antagonist of this pathway is predicted to be efficacious in a variety of hematologic malignancies. In vitro studies demonstrate that BMS-936564/MDX-1338 binds to CXCR4expressing cells with low nanomolar affinity. The antibody blocks CXCL12 binding to CXCR4 expressing cells and inhibits CXCL12 induced migration and calcium flux with low nanomolar EC50 values. When given as monotherapy on established tumors, the antibody exhibits anti-tumor activity in multiple AML, NHL and MM xenograft models. BMS-936564/MDX-1338 is an IgG4 and thus does not elicit complement dependent cytotoxicity (CDC) or antibody dependent cell mediated cytotoxicity (ADCC). In vitro and in vivo studies suggest that BMS-936564/MDX-1338 induces apoptosis as one mechanism of tumor growth inhibition. Here we describe the in vitro and in vivo characterization and activities of BMS-936564/MDX-1338. Disclosures: Kuhne: Bristol-Myers Squibb: Employment. Mulvey:Bristol-Myers Squibb: Employment. Chen:Bristol-Myers Squibb: Employment. Pan:Bristol-Myers Squibb: Employment. Chong:Bristol-Myers Squibb: Employment. Niekro:Bristol-Myers Squibb: Employment. Kempe:Bristol-Myers Squibb: Employment. Henning:Bristol-Myers Squibb: Employment. Cohen:Bristol-Myers Squibb: Employment. Korman:Bristol-Myers Squibb: Employment. Cardarelli:Bristol-Myers Squibb: Employment.
Sub-wavelength microscopy with surface plasmons (2018)

An attractive feature of surface plasmons (SPs) is the sub-wavelength characteristics, especially the SPs in two dimensional Dirac systems. In mid-infrared region, the wave vectors of graphene plasmons (GPs) can be two orders larger than that in vacuum, which have potential applications in optical imaging. Here, we propose a scheme that combining the GPs and structured illumination microscopy to realize a nanometer-scale microscopy. This scheme also takes advantage of the other two exciting properties of GPs, <i>i.e.</i>, tunability and low loss. The microscopy works in the linear regime and can be used in bioimaging.
Virus-like particles derived from Pichia pastoris-expressed dengue virus type 1 glycoprotein elicit homotypic virus-neutralizing envelope domain III-directed antibodies (2016)

This work demonstrates the inherent potential of P. pastoris-expressed DENV-1 E glycoprotein to self-assemble into VLPs eliciting predominantly homotypic neutralizing antibodies. This work justifies an investigation of the last remaining serotype, namely, DENV-4, to assess if it also shares the desirable vaccine potential manifested by the remaining three DENV serotypes. Such efforts could make it possible to envisage the development of a tetravalent dengue vaccine based on VLPs of P. pastoris-expressed E glycoproteins of the four DENV serotypes.
Continuous-flow, electrically-triggered, single cell-level electroporation (2017)

Electroporation creates transient openings in the cell membrane, allowing for intracellular delivery of diagnostic and therapeutic substances. The degree of cell membrane permeability during electroporation plays a key role in regulating the size of the delivery payload as well as the overall cell viability. A microfluidic platform offers the ability to electroporate single cells with impedance detection of membrane permeabilization in a high-throughput, continuous-flow manner. We have developed a flow-based electroporation microdevice that automatically detects, electroporates, and monitors individual cells for changes in permeability and delivery. We are able to achieve the advantages of electrical monitoring of cell permeabilization, heretofore only achieved with trapped or static cells, while processing the cells in a continuous-flow environment. We demonstrate the analysis of membrane permeabilization on individual cells before and after electroporation in a continuous-flow environment, which dramatically increases throughput. We have confirmed cell membrane permeabilization by electrically measuring the changes in cell impedance from electroporation and by optically measuring the intracellular delivery of a fluorescent probe after systematically varying the electric field strength and duration and correlating the pulse parameters to cell viability. We find a dramatic change in cell impedance and propidium iodide (PI) uptake at a pulse strength threshold of 0.87 kV/cm applied for a duration of 1 ms or longer. The overall cell viability was found to vary in a dose dependent manner with lower viability observed with increasing electric field strength and pulse duration. Cell viability was greater than 83% for all cases except for the most aggressive pulse condition (1[Formula: see text]kV/cm for 5[Formula: see text]ms), where the viability dropped to 67.1%. These studies can assist in determining critical permeabilization and molecular delivery parameters while preserving viability.
Enzymatic hydrolysis of Norway spruce and sugarcane bagasse after treatment with 1‐allyl‐3‐methylimidazolium formate (2013)

Abstract BACKGROUND Enzymatic hydrolysis of cellulose in lignocellulosic materials suffers from slow reaction rates due to limited access to enzyme adsorption sites and to the high crystallinity of the cellulose. In this study, an attempt was made to facilitate enzymatic hydrolysis by pretreatment of cellulosic materials using the ionic liquid ( IL ) 1‐allyl‐3‐methylimidazolium formate ([Amim][HCO2]) under mild reaction conditions. The effect of the IL was compared with that of thermochemical pretreatment under acidic conditions . RESULTS The lignocellulosic substrates investigated were native and thermochemically pretreated Norway spruce and sugarcane bagasse. Microcrystalline cellulose (Avicel) was included for comparison. The IL treatments were performed in the temperature range 45–120 °C and, after regeneration and washing of the cellulosic substrates, enzymatic saccharification was carried out at 45 °C for 72 h. After 12 h of hydrolysis, the glucose yields from regenerated native spruce and sugarcane bagasse were up to nine times higher than for the corresponding untreated substrates. The results also show positive effects of pretreatment using [Amim][HCO2] on the hydrolysis of xylan and mannan . Conclusion The present work demonstrates that both native wood and agricultural residues are readily soluble in [Amim][HCO2] under gentle conditions, and that pretreatment with ionic liquids such as [Amim][HCO2] warrants further attention as a potential alternative to conventional pretreatment techniques. © 2013 Society of Chemical Industry
A Novel Pyrazolo[1,5-<i>a</i>]pyrimidine Is a Potent Inhibitor of Cyclin-Dependent Protein Kinases 1, 2, and 9, Which Demonstrates Antitumor Effects in Human Tumor Xenografts Following Oral Administration (2010)

Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene expression. Abnormalities in CDK activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Here, we report the identification of a pyrazolo[1,5-a]pyrimidine derived compound, 4k (BS-194), as a selective and potent CDK inhibitor, which inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC₅₀= 3, 30, 30, 250, and 90 nmol/L, respectively). Cell-based studies showed inhibition of the phosphorylation of CDK substrates, Rb and the RNA polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G₂/M phases. Consistent with these findings, 4k demonstrated potent antiproliferative activity in 60 cancer cell lines tested (mean GI₅₀= 280 nmol/L). Pharmacokinetic studies showed that 4k is orally bioavailable, with an elimination half-life of 178 min following oral dosing in mice. When administered at a concentration of 25 mg/kg orally, 4k inhibited human tumor xenografts and suppressed CDK substrate phosphorylation. These findings identify 4k as a novel, potent CDK selective inhibitor with potential for oral delivery in cancer patients.
Learning the structure of task-driven human-human dialogs (2006)

Data-driven techniques have been used for many computational linguistics tasks. Models derived from data are generally more robust than hand-crafted systems since they better reflect the distribution of the phenomena being modeled. With the availability of large corpora of spoken dialog, dialog management is now reaping the benefits of data-driven techniques. In this paper, we compare two approaches to modeling subtask structure in dialog: a chunk-based model of subdialog sequences, and a parse-based, or hierarchical, model. We evaluate these models using customer agent dialogs from a catalog service domain.
Pteridine Analysis in Urine by Capillary Electrophoresis Using Laser-Induced Fluorescence Detection (1999)

Pteridines are a class of compounds excreted in urine, the levels of which are found to elevate significantly in tumor-related diseases. For the first time, we have developed a method, based on high-performance capillary electrophoresis (HPCE) and laser-induced fluorescence (LIF) detection, to monitor the pteridine levels in urine. HPCE provides better separation than high-performance liquid chromatography and the LIF detector enables us to detect minute amounts of pteridines in body fluid. Eight different pteridine derivatives were well separated in 0.1 M Tris-0.1 M borate-2 mM EDTA buffer (pH 8.75) using a 60-cm fused-silica capillary (50-micron i.d., 35-cm effective length), six of which were detected and characterized in urine samples from normal persons and different cancer patients. The detection limits of these pteridines are under 1 x 10(-10) M. The levels of neopterin, pterine, xanthopterin, and pterin-6-carboxylic acid were found to be significantly elevated in urine excreted by cancer patents, while the level of isoxanthopterin dropped in these patients. No significant change of biopterin level was found between healthy individuals and cancer patients. This method can be used in clinical laboratories either for cancer monitoring or for precancer screening.
A New Contrast Sensitivity Test for Pediatric Patients: Feasibility and Inter-Examiner Reliability in Ocular Disorders and Cerebral Visual Impairment (2020)

CS and VA both should be tested in pediatric clinical populations, especially in those at risk of CVI.
Late-Stage Intermolecular Allylic C–H Amination (2021)

Allylic amination enables late-stage functionalization of natural products where allylic C-H bonds are abundant and introduction of nitrogen may alter biological profiles. Despite advances, intermolecular allylic amination remains a challenging problem due to reactivity and selectivity issues that often mandate excess substrate, furnish product mixtures, and render important classes of olefins (for example, functionalized cyclic) not viable substrates. Here we report that a sustainable manganese perchlorophthalocyanine catalyst, [Mn<sup>III</sup>(ClPc)], achieves selective, preparative intermolecular allylic C-H amination of 32 cyclic and linear compounds, including ones housing basic amines and competing sites for allylic, ethereal, and benzylic amination. Mechanistic studies support that the high selectivity of [Mn<sup>III</sup>(ClPc)] may be attributed to its electrophilic, bulky nature and stepwise amination mechanism. Late-stage amination is demonstrated on five distinct classes of natural products, generally with >20:1 site-, regio-, and diastereoselectivity.