gebhart/patrepeval huggingface dataset:
Mass spectrometry of intact complexes of benzyl styryl sulfone ON1910Na with albumin using direct serum injection (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3099 

The benzyl styryl sulfone analog (ON1910Na, 473.5 Da) is currently in Phase I clinical trials. The objective was to characterize the intact complexes formed between drug and serum albumin in treated mice and in patients. Molecular masses indicated the number of drug molecules in the complex at various dose levels and sampling times. Serum and plasma were obtained from treated mice with various solid tumors and patients. One μL aliquots were injected directly into the mass spectrometer. Positive electrospray mass spectra were obtained with a triple quadrupole instrument. Molecular masses of the intact drug-albumin complexes were obtained from multiple charged ion patterns, based on the interrupted incremental augmentation of albumin masses, using conventional transformation software. Unbound 1910Na was quantified by selected reaction monitoring (m/z 474 to 216 transition). Complex formation between the drug and albumin commenced immediately upon exposure. The smooth lines of the bell-shaped multiply charged ion patterns of serum albumin became ragged. The molecular masses of the intact complexes and the number of bound drug molecules could be determined from the new peaks. Masses were determined to 0.1%. Data from mouse and human samples were comparable but not the same. Up to 21 drug molecules were bound per albumin molecule depending upon drug dose, quantity of unbound drug, and time of sampling. The number of drug molecules added were discontinuous, suggesting conformational changes permitting certain numbers of drug molecules to bind but excluding others. The technique developed demonstrates that free drug concentration and drug-albumin binding data can be measured directly in untreated serum or plasma, thus avoiding iatrogenic artifacts. (Supported by the T. J. Martell Foundation for Leukemia, Cancer and AIDS Research and by Onconova Therapeutics, Inc.).
Induction of effective and antigen-specific antitumour immunity by a liposomal ErbB2/HER2 peptide-based vaccination construct (2005)

Efficient delivery of tumour-associated antigens to appropriate cellular compartments of antigen-presenting cells is of prime importance for the induction of potent, cell-mediated antitumour immune responses. We have designed novel multivalent liposomal constructs that co-deliver the p63-71 cytotoxic T Lymphocyte epitope derived from human ErbB2 (HER2), and HA307-319, a T-helper (Th) epitope derived from influenza haemagglutinin. Both peptides were conjugated to the surface of liposomes via a Pam3CSS anchor, a synthetic lipopeptide with potent adjuvant activity. In a murine model system, vaccination with these constructs completely protected BALB/c mice from subsequent s.c. challenge with ErbB2-expressing, but not ErbB2-negative, murine renal carcinoma (Renca) cells, indicating the induction of potent, antigen-specific immune responses. I.v. re-challenge of tumour-free animals 2 months after the first tumour cell inoculation did not result in the formation of lung tumour nodules, suggesting that long-lasting, systemic immunity had been induced. While still protecting the majority of vaccinated mice, a liposomal construct lacking the Th epitope was less effective than the diepitope construct, also correlating with a lower number of CD8+ IFN-gamma+ T-cells identified upon ex vivo peptide restimulation of splenocytes from vaccinated animals. Importantly, in a therapeutic setting treatment with the liposomal vaccines resulted in cures in the majority of tumour-bearing mice and delayed tumour growth in the remaining ones. Our results demonstrate that liposomal constructs which combine Tc and Th peptide antigens and lipopeptide adjuvants can induce efficient, antigen-specific antitumour immunity, and represent promising synthetic delivery systems for the design of specific antitumour vaccines.
Extreme States Distribution Decomposition Method for Search Engine Online Evaluation (2015)

Nowadays, the development of most leading web services is controlled by online experiments that qualify and quantify the steady stream of their updates. The challenging problem is to define an appropriate online metric of user behavior, so-called Overall Evaluation Criterion (OEC), which is both interpretable and sensitive. The state-of-the-art approach is to choose a type of entities to observe in the behavior data, to define a key metric for these observations, and to estimate the average value of this metric over the observations in each of the system versions. A significant disadvantage of the OEC obtained in this way is that the average value of the key metric does not necessarily change, even if its distribution changes significantly. The reason is that the difference between the mean values of the key metric over the two variants of the system does not necessarily reflect the character of the change in the distribution.
Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly (2006)

Ribonucleotide reductase (RNR) catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates. Crucial for rapidly dividing cells, RNR is a target for cancer therapy. In eukaryotes, RNR comprises a heterooligomer of alpha(2) and beta(2) subunits. Rnr1, the alpha subunit, contains regulatory and catalytic sites; Rnr2, the beta subunit (in yeast, a heterodimer of Rnr2 and Rnr4), houses the diferric-tyrosyl radical crucial for catalysis. Here, we present three x-ray structures of eukaryotic Rnr1 from Saccharomyces cerevisiae: one bound to gemcitabine diphosphate (GemdP), the active metabolite of the mechanism-based chemotherapeutic agent gemcitabine; one with an Rnr2-derived peptide, and one with an Rnr4-derived peptide. Our structures reveal that GemdP binds differently from its analogue, cytidine diphosphate; because of unusual interactions of the geminal fluorines, the ribose and base of GemdP shift substantially, and loop 2, which mediates substrate specificity, adopts different conformations when binding to GemdP and cytidine diphosphate. The Rnr2 and Rnr4 peptides, which block RNR assembly, bind differently from each other but have unique modes of binding not seen in prokaryotic RNR. The Rnr2 peptide adopts a conformation similar to that previously reported from an NMR study for a mouse Rnr2-based peptide. In yeast, the Rnr2 peptide binds at subsites consisting of residues that are highly conserved among yeast, mouse, and human Rnr1s, suggesting that the mode of Rnr1-Rnr2 binding is conserved among eukaryotes. These structures provide new insights into subunit assembly and a framework for structure-based drug design targeting RNR.
Language independent and unsupervised acoustic models for speech recognition and keyword spotting (2014)

Copyright © 2014 ISCA. Developing high-performance speech processing systems for low-resource languages is very challenging. One approach to address the lack of resources is to make use of data from multiple languages. A popular direction in recent years is to train a multi-language bottleneck DNN. Language dependent and/or multi-language (all training languages) Tandem acoustic models (AM) are then trained. This work considers a particular scenario where the target language is unseen in multi-language training and has limited language model training data, a limited lexicon, and acoustic training data without transcriptions. A zero acoustic resources case is first described where a multilanguage AM is directly applied, as a language independent AM (LIAM), to an unseen language. Secondly, in an unsupervised approach a LIAM is used to obtain hypotheses for the target language acoustic data transcriptions which are then used in training a language dependent AM. 3 languages from the IARPA Babel project are used for assessment: Vietnamese, Haitian Creole and Bengali. Performance of the zero acoustic resources system is found to be poor, with keyword spotting at best 60% of language dependent performance. Unsupervised language dependent training yields performance gains. For one language (Haitian Creole) the Babel target is achieved on the in-vocabulary data.
Optical pickup for recording to dual-layer high-speed blu-ray disc (2007)

A compact BD optical system with high light use efficiency that enables high-speed recording to a dual-layer BD is reviewed. It also achieves stable tracking-error detection on a dual-layer BD using a stray-light-free one-beam method.
Broadband omnidirectional antenna for GSM900, GSM1800, 3G, 4G and Wi-Fi applications (2017)

In this paper, a broadband omnidirectional antenna, consisting of three tapered monopoles is presented. The antenna has |S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> | <; -10dB from 880MHz to 2.52GHz. The gain of the antenna is greater than 2dBi over the entire bandwidth. The measured H-plane radiation pattern is omnidirectional with less than 8dB variation over the entire bandwidth. The antenna covers GSM900, GSM1800, 3G, 4G and Wi-Fi bands.
Transform domain LMF algorithm for sparse system identification under low SNR (2015)

In this work, a transform domain Least Mean Fourth (LMF) adaptive filter for a sparse system identification, in the case of low Signal-to-Noise Ratio (SNR), is proposed. Unlike the Least Mean Square (LMS) algorithm, the LMF algorithm, because of its error nonlinearity, performs very well in these environments. Moreover, its transform domain version has an outstanding performance when the input signal is correlated. However, it lacks sparse information capability. To overcome this limitation, a zero attractor mechanism, based on the l <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> norm is implemented to yield the Zero-Attractor Transform-Domain LMF (ZA-TD-LMF) algorithm. The ZA-TD-LMF algorithm ensures fast convergence and attracts all the filter coefficients to zero. Simulation results conducted to substantiate our claim are found to be very effective.
Measurements of spin correlation in top-antitop quark events from proton-proton collisions at √s = 7 TeV using the ATLAS detector (2014)

Measurements of spin correlation in top quark pair production are presented using data collected with the ATLAS detector at the LHC with proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 4.6 fb-1. Events are selected in final states with two charged leptons and at least two jets and in final states with one charged lepton and at least four jets. Four different observables sensitive to different properties of the top quark pair production mechanism are used to extract the correlation between the top and antitop quark spins. Some of these observables are measured for the first time. The measurements are in good agreement with the Standard Model prediction at next-to-leading-order accuracy.
Prognostic value of delayed enhancement cardiovascular magnetic resonance in patients with sarcoidosis (2012)

In patients with sarcoidosis, myocardial involvement by DE-CMR is the strongest independent predictor of adverse cardiac prognosis.
Cryospectrokinetic characterization of intermediates in biochemical reactions: carboxypeptidase A. (1984)

Cryospectrokinetic studies provide concurrent structural, kinetic, and chemical data on short-lived intermediates in the course of the interactions of enzymes with their substrates and of other, similar pairs of biomolecules. Subzero temperatures extend the lifetimes of these intermediates and, combined with rapid-mixing and rapid-scanning instrumentation, allow simultaneous measurement of both their physical-chemical and kinetic characteristics. For carboxypeptidase A, the spectra of a chromophoric, enzymatically functional cobalt atom at the active site signal the structure of the coordination complex during catalysis, while radiationless energy transfer between enzyme tryptophans and the fluorescent dansyl blocking group of rapidly hydrolyzed peptide and ester substrates provides the basis for measurement of the rates of formation and breakdown of intermediates. Subzero radiationless energy transfer kinetic studies of the zinc and cobalt enzymes disclose two intermediates in the hydrolysis of both peptides and esters and furnish all the rate and equilibrium constants for the reaction scheme E + S in equilibrium ES1 in equilibrium ES2----E + P. The chemical and kinetic data indicate that neither of these is an acylenzyme intermediate. Both absorption and EPR spectra of the ES2 reaction intermediates consistently demonstrate the formation of transient metal complexes, differences between the effects induced by peptides and esters, and strong similarities between those induced by all peptides on the one hand and all esters on the other. The marked alterations of the cobalt spectra likely reflect the coordination of a substrate carboxyl and/or carbonyl group to the metal at a critical step in the course of catalysis. The cryospectrokinetic approach developed here in the mechanistic study of this metalloenzyme is applicable to the examination of transients of biochemical reactions in general. It will allow molecular characterization of previously elusive intermediates and greatly magnify the range of mechanistic questions that can be answered.
Proteomic analysis of EZH2 downstream target proteins in hepatocellular carcinoma (2007)

Enhancer of zeste homolog 2 (EZH2) is suggested to be a potential therapeutic target and a diagnostic marker for cancer. Our previous study also showed the critical role of EZH2 in hepatocellular carcinoma (HCC) tumorigenesis. The present study is aimed at revealing the comprehensive downstream pathways of EZH2 by functional proteomic profiling. Lentivirus mediated RNA interference (RNAi) was employed to knockdown EZH2 in HCC cells. The 2-DE was employed to compare the expression profile difference between parental and EZH2-knockdown HCC cells. In total, 28 spots were differentially expressed during EZH2 inhibition. Among all, 18 proteins were identified by PMF with MALDI-TOF MS. Western blotting further validated upregulation of 60S acidic ribosomal protein P0 (L10E), and downregulation of two proteins with EZH2 inhibition: stathmin1 and probable protein disulfide isomerase (PDI) ER-60 precursor (ERp57). Moreover, L10E was downregulated with overexpression of EZH2 in hepatocytes, and L10E reversed the effect of EZH2 on cell proliferation, suggesting it a downstream target of EZH2. The comprehensive and comparative analyses of proteins associated with EZH2 could further our understanding on the downstream signal cascade of EZH2 leading to tumorigenesis.
3‐carboxy‐4‐nitrophenyl‐dithio‐1,1′,2‐trisnorsqualene: A site‐directed inactivator of yeast oxidosqualene cyclase (1993)

The role and location of essential thiol groups in 2,3-oxidosqualene cyclase from Saccharomyces cerevisiae was examined (i) by comparing inactivation properties of two known thiol reagents, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and 2-nitro-5-thiocyanobenzoic acid (NTCB), with 3-carboxy-4-nitrophenyl-dithio-1,1',2-trisnorsqualene (CNDT-squalene), a new thiol reagent designed as a site-directed inactivator of oxidosqualene cyclase and (ii) by testing the ability of the substrate to protect the enzyme against inactivation by the reagents. All reagents gave a time-dependent inactivation following pseudo-first order kinetics. DTNB and CNDT-squalene showed comparable inactivation ability (Ki = 0.67 and 1.21 mM), whereas NTCB was less effective (Ki = 15.6 mM). Strong differences between the two most active inhibitors, DTNB and CNDT-squalene, were observed when the enzyme was saturated with substrate prior to incubation with the thiol reagent. While substrate did not protect the enzyme against the inactivation caused by DTNB, a reduction in the inactivation ability of CNDT-squalene was observed under protection conditions. The data suggest that the squalene-like inactivator modifies a thiol group located at the active site of the enzyme.
Targeting Myocardial Remodelling to Develop Novel Therapies for Heart Failure (2014)

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/endoplasmic Ca(2 +) ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.
Model-Predictive Control of Discrete Hybrid Stochastic Automata (2010)

This paper focuses on optimal and receding horizon control of a class of hybrid dynamical systems, called Discrete Hybrid Stochastic Automata (DHSA), whose discrete-state transitions depend on both deterministic and stochastic events. A finite-time optimal control approach “optimistically” determines the trajectory that provides the best tradeoff between tracking performance and the probability of the trajectory to actually execute, under possible chance constraints. The approach is also robustified, less optimistically, to ensure that the system satisfies a set of constraints for all possible realizations of the stochastic events, or alternatively for those having enough probability to realize. Sufficient conditions for asymptotic convergence in probability are given for the receding-horizon implementation of the optimal control solution. The effectiveness of the suggested stochastic hybrid control techniques is shown on a case study in supply chain management.
Bacterial messages to Eukaryotes (2012)

Symbiotic relationships involving microbes and eukaryotes come in many flavors as all eukaryotes have spent their entire evolutionary history on a planet teeming with microbes, and the two have evolved many ways of dealing with each other. This lecture will describe the small molecule chemistry that regulates a particularly complicated symbiotic relationship between bacteria belonging to the roseobacter clade and the microscopic alga Emiliana huxleyi and some of its relatives. The relationship is complicated because it changes with time as the bacterial chemistry responds to variable signals sent by their algal partner. The talk will involve three related topics, and the first is the isolation and structures of the bacterially produced roseobacticides, a group of roughly a dozen characterized molecules – and many more remaining to be characterized – with unusual structures as illustrated by roseobacticides A, B and C shown below.
Nano-sized structured layered positive electrode materials to enable high energy density and high rate capability lithium batteries (2023)

Nano-sized structured dense and spherical layered positive active materials provide high energy density and high rate capability electrodes in lithium-ion batteries. Such materials are spherical second particles made from agglomerated primary particles that are Li.sub.1+.alpha.(Ni.sub.xCo.sub.yMn.sub.z).sub.1-tM.sub.tO.sub.2-dR.sub.d- , where M is selected from can be Al, Mg, Fe, Cu, Zn, Cr, Ag, Ca, Na, K, In, Ga, Ge, V, Mo, Nb, Si, Ti, Zr, or a mixture of any two or more thereof, R is selected from F, Cl, Br, I, H, S, N, or a mixture of any two or more thereof, and 0.ltoreq..alpha..ltoreq.0.50; 0&lt;x.ltoreq.1; 0.ltoreq.y.ltoreq.1; 0&lt;z.ltoreq.1; 0.ltoreq.t.ltoreq.1; and 0.ltoreq.d.ltoreq.0.5. Methods of preparing such materials and their use in electrochemical devices are also described.
Stereospecific Approach to the Synthesis of Ring-A Oxygenated Sarpagine Indole Alkaloids. Total Synthesis of the Dimeric Indole Alkaloid P-(+)-Dispegatrine and Six Other Monomeric Indole Alkaloids (2013)

The first regio- and stereocontrolled total synthesis of the bisphenolic, bisquaternary alkaloid (+)-dispegatrine (1) has been accomplished in an overall yield of 8.3% (12 reaction vessels) from 5-methoxy-d-tryptophan ethyl ester (17). A crucial late-stage thallium(III) mediated intermolecular oxidative dehydrodimerization was employed in the formation of the C9-C9' biaryl axis in 1. The complete stereocontrol observed in this key biaryl coupling step is due to the asymmetric induction by the natural sarpagine configuration of the monomer lochnerine (6) and was confirmed by both the Suzuki and the oxidative dehydrodimerization model studies on the tetrahydro β-carboline (35). The axial chirality of the lochnerine dimer (40) and in turn dispegatrine (1) was established by X-ray crystallography and was determined to be P(S). Additionally, the first total synthesis of the monomeric indole alkaloids (+)-spegatrine (2), (+)-10-methoxyvellosimine (5), (+)-lochnerine (6), lochvinerine (7), (+)-sarpagine (8), and (+)-lochneram (11) were also achieved via the common pentacyclic intermediate 16.
A 10 nV/rt Hz noise level 32-channel neural impedance sensing ASIC for local activation imaging on nerve section (2020)

A 10 nV/rt Hz noise level 32-channel neural impedance sensing ASIC is presented for the application of local activation imaging in nerve section. It is increasingly known that the monitoring and control of nerve signals can improve physical and mental health. Major nerves, such as the vagus nerve and the sciatic nerve, consist of a bundle of fascicles. Therefore, to accurately control a particular application without any side effects, we need to know exactly which fascicle was activated. The only way to find locally activated fascicle is to use electrical impedance tomography (EIT). The ASIC to be introduced is designed for neural EIT applications. A neural impedance sensing ASIC was implemented using CMOS 180-nm process technology. The integrated input referred noise was calculated to be 0.46 μVrms (noise floor 10.3 nVrms/rt Hz) in the measured noise spectrum. At an input of 80 mV, the squared correlation coefficient for linear regression was 0.99998. The amplification gain uniformity of 32 channels was in the range of + 0.23% and - 0.29%. Using the resistor phantom, the simplest model of nerve, it was verified that a single readout channel could detect a signal-to- noise ratio of 75.6 dB or more. Through the reservoir phantom, real-time EIT images were reconstructed at a rate of 8.3 frames per second. The developed ASIC has been applied to in vivo experiments with rat sciatic nerves, and signal processing is currently underway to obtain activated nerve cross-sectional images. The developed ASIC was also applied to in-vivo experiments with rat sciatic nerves, and signal processing is currently underway to obtain locally activated nerve cross-sectional images.