gebhart/patrepeval huggingface dataset:
Elucidation of the metabolic and elimination pathways of panobinostat (LBH589) using [14C]-panobinostat (2009)

2549 Background: Panobinostat (PAN), a hydroxamic acid derivative, is a potent pan-deacetylase inhibitor, demonstrating anti-tumor activities in a wide variety of preclinical models and showing promising clinical activity. This study elucidates the metabolic and elimination pathways of PAN using [ 14 C]-PAN. Methods: Four patients with advanced cancer received a single oral 20 mg dose of [ 14 C]-PAN (50 μCi). Whole blood, plasma, urine, and feces were collected over 7 days. Total radioactivity was measured in blood, plasma, and excreta by liquid scintillation counting. PAN and its metabolite concentrations in plasma and excreta were measured by LC-MS/MS and HPLC with radiometric detection. Patients were monitored for safety. Results: The single PAN dose was well tolerated with no clinically significant laboratory or ECG abnormalities observed. PAN had a rapid oral absorption [median T max 0.8 h (range, 0.5–1 h)] and moderate elimination (median t 1/2 31 h). The median t 1/2 for blood and plasma radioactivity was 54 and 75 hours, respectively. Mass balance was achieved with ≥87% of the administered radioactivity being recovered in the excreta of all patients after 7 days. 44–77% and 29–51% of the dose was recovered in the feces and urine, respectively. Unchanged PAN accounted for ≤3% of the administered dose in the feces, suggesting good oral absorption. The most prominent metabolic pathways involved modifications of the hydroxamic acid (HA) side chain, to form an amide via reduction, carboxylic acid via either hydrolysis or one- and two-carbon (M1) shortening of the HA side chain. Oxygenation and glucuronidation were also observed. PAN accounted for ≤9% of the total radioactivity AUC. The most abundant circulating metabolites in plasma were the glucuronide of M1 (19%) and carbamoyl glucuronide of PAN (13%). At least 40 metabolites, many at trace levels, were observed circulating in plasma. Conclusions: PAN and its metabolites are equally excreted in the urine and feces. Elimination of PAN is primarily by metabolism via reduction, hydrolysis, oxidation and glucuronidation. The balanced elimination and absence of a single major route of PAN metabolism suggest that clinical drug-drug interactions are unlikely with PAN. [Table: see text]
On MIMO with successive interference cancellation applied to UTRA LTE (2008)

The long term evolution of UMTS (Universal Mobile Telecommunications System) Terrestrial Radio Access, abbreviated as UTRA LTE, makes use of OFDM (orthogonal frequency division multiplexing) combined with MIMO (multiple-input multiple-output), termed MIMO-OFDM. The potential maximization of transmitted data rates has been considered a most beneficial feature of MIMO schemes. This maximization shall be strived for by spatial multiplexing. In particular, high data rates in the downlink have been considered desirable. Also, in view of an efficient implementation, the downlink requires a thorough assessment. Therefore, the authors will discuss the deployment of spatial multiplexing in the UTRA LTE downlink and will show that the performance of successive interference cancellation (SIC) based data detection techniques for MIMO-OFDM is beneficial.
Conformational studies of metal chelates. II. Stereochemistry and conformational analysis of the cobalt(III) complexes of 4,7-diaza-5(R)-methyl-1,10-decanediamine (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformational studies of metal chelates. II. Stereochemistry and conformational analysis of the cobalt(III) complexes of 4,7-diaza-5(R)-methyl-1,10-decanediamineLouis J. DeHayes and Daryle H. BuschCite this: Inorg. Chem. 1973, 12, 9, 2010–2015Publication Date (Print):September 1, 1973Publication History Published online1 May 2002Published inissue 1 September 1973https://pubs.acs.org/doi/10.1021/ic50127a012https://doi.org/10.1021/ic50127a012research-articleACS PublicationsRequest reuse permissionsArticle Views40Altmetric-Citations11LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Antagonism of acute cocaine toxicity by buprenorphine (1991)

The effect of buprenorphine pretreatment on the acute cocaine toxicity was assessed in male Swiss Webster mice. Buprenorphine pretreatment (0.15 or 0.30 mg/kg ip, 30 mins before) significantly attenuated the lethal effects of cocaine (60-140 mg/kg ip). The dose of cocaine which resulted in 50% mortality (LD50) in saline pretreated group was 100.61 mg/kg while the LD50 of cocaine in buprenorphine (0.15 and 0.3 mg/kg) pretreated groups were 113.57 and 118.16 mg/kg respectively. There was no significant change in the ratio of brain/plasma levels of cocaine in buprenorphine pretreated group when compared to the ratio from saline treated controls. Furthermore, neither naloxone (10 mg/kg ip, 15 mins before) nor naltrexone (3 mg/kg ip, 15 mins before) pretreatment affected the LD50 of cocaine. When tested 0.5, 1, 2, 4, 8 and 24 hrs after cocaine administration, sublethal dose of cocaine (80 mg/kg ip) injection resulted in significant increase in the plasma lactate dehydrogenase (LDH) levels. Buprenorphine pretreatment significantly attenuated cocaine-induced release of LDH. These results suggest that buprenorphine could be of potential advantage over naloxone in the management of cocaine and heroin ("speed ball") toxicity and in studies on the pharmacotherapy of cocaine-induced toxicity, LDH levels may be used as a biochemical marker to assess the protective effects of drugs.
Frequency domain selective tap adaptive algorithms for sparse system identification (2008)

We propose a new low complexity and fast converging frequency-domain adaptive algorithm for sparse system identification. This is achieved by exploiting the MMax and SP tap-selection criteria for complexity reduction and fast convergence respectively. We incorporate these tap-selection techniques into the multi-delay filtering (MDF) algorithm in order to reduce the delay inherent in frequency-domain algorithms. We illustrate two such approaches and discuss the tradeoff between convergence performance and computational complexity for these approaches. Simulation results show an improvement in convergence rate for the proposed algorithm over MDF with reduced complexity. The proposed algorithm achieves a convergence performance close to that of the recently proposed but substantially more complex improved proportionate MDF algorithm.
INCIDENCE AND CHARACTERISTICS OF NEOVASCULARIZATION IN FELLOW EYES OF JAPANESE PATIENTS WITH UNILATERAL RETINAL ANGIOMATOUS PROLIFERATION (2013)

Bilateral RAP developed in almost half of the eyes initially diagnosed with unilateral RAP and the incidence increased with time. Reticular pseudodrusen is a risk factor for bilateral RAP.
IR-assisted ionization of helium by attosecond extreme ultraviolet radiation (2010)

Attosecond science has opened up the possibility of manipulating electrons on the ir fundamental timescales. Here, we use both theory and experi- ment to investigate ionization dynamics in helium on the attosecond timescale by simultaneously irradiating the atom with a soft x-ray attosecond pulse train (APT) and an ultrafast lase rpulse. Because the APT has resolution in both energy and time,we observe processes that could not be observed without resolu- tion in both domains simultaneously. We show that resonant absorption is impor- tant in the excitation of helium and that small changes in energies of harmonics that comprise the APT can result in large changes in the ionization process. With the help of theory, ionization pathways for the infrared-assisted excitation and ionization of helium by extreme ultraviolet (XUV) attosecond pulses have been identi?ed and simple model interpretations have been developed that should be of general applicability to more complex systems (Zewail A 2000 J. Phys. Chem. A 1045660-94).
Direct and cost-efficient hyperpolarization of long-lived nuclear spin states on universal 15 N 2 -diazirine molecular tags (2016)

Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed method, SABRE-SHEATH, to directly hyperpolarize (15)N2 magnetization and long-lived (15)N2 singlet spin order, with signal decay time constants of 5.8 and 23 minutes, respectively. We find >10,000-fold enhancements generating detectable nuclear MR signals that last for over an hour. (15)N2-diazirines represent a class of particularly promising and versatile molecular tags, and can be incorporated into a wide range of biomolecules without significantly altering molecular function.
Human Immunodeficiency Virus in Semen and Plasma: Investigation of Sexual Transmission Risk Behavioral Correlates (2001)

Risks for sexually transmitted HIV may be related to concentrations of virus detected in semen and previous research shows a small to moderate association between viral load in blood and semen. This study examined the association between viral load in semen and plasma in a community sample of HIV-infected men and is the first study to examine semen viral load in relation to sexual transmission risk behaviors. A sample of 44 HIV-positive men recruited from community service agencies provided semen, blood, and urine samples and completed clinical interviews assessing health and behavior. We failed to find an association between viral load in semen and plasma, Spearman rho = 0.07, p > 0.1. When restricted to participants with detectable virus in semen and plasma, the correlation remained nonsignificant, rho = -0.16, p > 0.1. Men who had higher semen viral loads relative to their plasma viral load were distinguished by having engaged in significantly higher rates of unprotected intercourse as the insertive sex partner in the previous 3 months. Semen viral load was not, however, related to recent or current sexually transmitted infections (STIs). This study is among the first to examine sexual transmission risk behaviors as marker for HIV infectiousness. Results caution against inferring sexual transmission infectiousness based on plasma viral load and suggest that HIV-positive men who practice higher rates of insertive intercourse may be more infectious even in the absence of other STIs.
Arrays of topographically and peptide-functionalized hydrogels for analysis of biomimetic extracellular matrix properties (2012)

Epithelial cells reside on specialized extracellular matrices that provide instructive cues to regulate and support cell function. The authors have previously demonstrated that substrate topography with dimensions similar to the native extracellular matrix (submicrometer and nanoscale features) significantly impacts corneal epithelial proliferation and migration. In this work, synthetic hydrogels were modified with both topographic and biochemical cues, where specified peptide ligands were immobilized within nanopatterned hydrogels. The efficient, systematic study of multiple instructive cues (peptide, peptide concentration, topographic dimensions), however, is contingent on the development of higher throughput platforms. Toward this goal, the authors developed a hydrogel array platform to systematically and rapidly evaluate combinations of two different peptide motifs and a range of nanoscale topographic dimensions. Specifically, distinct functional pegylated peptide ligands, RGD (GGGRGDSP) and AG73 (GRKRLQVQLSIRT), were synthesized for incorporation into an inert hydrogel network. Elastomeric stencils with arrays of millimeter-scale regions were used to spatially confine hydrogel precursor solutions on elastomeric stamps with nanoscale patterns generated by soft lithography. The resulting topographically and peptide-functionalized hydrogel arrays were used to characterize single cell migration. Epithelial cell migration speed and persistence were governed by both the biochemical and topographical cues of the underlying substrate.
Scheduling and Aggregation Design for Asynchronous Federated Learning over Wireless Networks (2022)

Federated Learning (FL) is a collaborative machine learning (ML) framework that combines on-device training and server-based aggregation to train a common ML model among distributed agents. In this work, we propose an asynchronous FL design with periodic aggregation to tackle the straggler issue in FL systems. Considering limited wireless communication resources, we investigate the effect of different scheduling policies and aggregation designs on the convergence performance. Driven by the importance of reducing the bias and variance of the aggregated model updates, we propose a scheduling policy that jointly considers the channel quality and training data representation of user devices. The effectiveness of our channel-aware data-importance-based scheduling policy, compared with state-of-the-art methods proposed for synchronous FL, is validated through simulations. Moreover, we show that an ``age-aware'' aggregation weighting design can significantly improve the learning performance in an asynchronous FL setting.
Epoxy-Induced Spalling of Silicon (2012)

One of the main driving forces to lower the silicon solar cell modules overall cost is to decrease the thickness of the silicon substrate and, at same time, to reduce the material losses caused by the sawing of the silicon ingot. For this reason, a considerable number of methods have been proposed in the last decade to manufacture thin silicon foils which aim to replace the commonly used sawing technique. One of these methods is based on peeling off a thin layer from a silicon substrate by means of the residual stress induced either through the only deposition of a layer on a silicon substrate or through a succeeding thermal cycle of such a bilayer. Up to now, three different materials have been successfully employed in this technique: Nickel, Nickel/Chromium alloy and a Silver/Aluminium system. In this work we demonstrate the possibility to induce the lift-off of a thin silicon foil by means of curing an epoxy layer on top of a silicon wafer. This new method has the advantages of reducing metal contamination in the silicon and lowers the operating temperatures below 150°C.
Enhanced polarization-independent optical ring resonators on silicon-on-insulator (2005)

Recently, we have realised a polarisation independent optical racetrack resonator whose resonant dips for TE and TM align to better than 1pm. The devices had a Free Spectral Range (FSR) of only several hundred picometres. This in large part was to the relatively large bend radius (~ 400μm) designed and fabricated with initial focus on producing low bend loss devices. Modelling of the bend loss of the same dimension devices shows that the bend radius can be reduced significantly (down to ~25μm) to produce race track ring resonator with an FSR that is approximately 400% larger than that of those previously fabricated, whilst retaining polarisation independence. This paper will focus on the proposed enhancement of these devices as well as the impetus for their investigation.
Influence of background noise and microphone on the performance of the IBM Tangora speech recognition system (1993)

With the intention of developing a robust speech recognizer largely immune to the vagaries of extrinsic changes, the authors investigated the effects of various background noises and microphones on the performance of the Tangora system. They identified several noisy locations such as the cafeteria and a secretary's office and included a relatively quiet office for comparison. They recorded isolated-word training and test data from one male and one female speaker at different locations employing several varieties of microphones. A typical experiment consisted of designing a speaker-independent HMM (hidden Markov model) system with one set of training data and decoding the test data collected at all locations. It was found that microphone characteristics had a significant impact on the robustness of the system. It was also observed that controlled contamination of the quiet training data with ambient noise improved the noise immunity of the recognizer, discounting the role of the Lombard effect in the studies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Dynamic texture segmentation (2017)

We address the problem of segmenting a sequence of im-ages of natural scenes into disjoint regions that are charac-terized by constant spatio-temporal statistics. We model the spatio-temporal dynamics in each region by Gauss-Markov models, and infer the model parameters as well as the boundary of the regions in a variational optimization frame-work. Numerical results demonstrate that – in contrast to purely texture-based segmentation schemes – our method is effective in segmenting regions that differ in their dynamics even when spatial statistics are identical. 1.
Abstract 1136: Targeting DHX9 inhibition as a novel therapeutic modality in microsatellite instable colorectal cancer (2023)

Abstract DHX9 is a multifunctional DEAH-box ATP-independent RNA helicase which has been reported to play important roles in replication, transcription, translation, RNA splicing and RNA processing which contribute to DHX9’s role in maintenance of genomic stability. Functionally, DHX9’s role involves binding to as well as unwinding and/or resolving double-stranded and single-stranded DNA/RNA, DNA/RNA hybrids (R-loops), circular RNA and DNA/RNA G quadraplexes. Overexpression of DHX9 is evident in multiple cancer types, including colorectal cancer (CRC) and lung cancer. In addition, microsatellite instable (MSI) tumors exhibiting defective mismatch repair (dMMR) show a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery. Here we describe data supporting targeting DHX9 in MSI CRC as a novel therapeutic, and the first identification of potent and selective in vitro and in vivo small molecule inhibitors of DHX9. We demonstrate that DHX9 inhibition in MSI CRC, delivered either through siRNA knockdown or compound treatment, leads to an increase in RNA/DNA secondary structures such as R-loops and circRNA (i.e. circBRIP1) inducing replication stress. Cell lines that are dMMR (i.e. MSI) are unable to resolve this replication stress, resulting in prevention of DNA replication in S phase and later onset of apoptosis. We were able to confirm this selective dependency in a panel of 20 CRC cell lines; anti-proliferative effects mediated by DHX9 inhibition were dependent on cell line dMMR status in a 10-day proliferation assay. Furthermore, compound 1, an orally bioavailable DHX9 inhibitor was used to investigate in vivo efficacy in MSI CRC (LS411N) and MSS CRC (SW480) xenograft models. Compound 1 was well tolerated across the 28-day treatment period with robust and durable tumor regression (TGI = 105 %) observed in the LS411N tumor xenograft model only. In addition, following cessation of treatment, minimal tumor regrowth was observed in a 28-day post treatment window. Tumor and plasma concentrations of compound 1 and changes in pharmacodynamic markers of DHX9 inhibition, such as circBRIP1 mRNA, were measured and resulting PK and PD data were highly correlated. Together, these preclinical data validate DHX9 as a tractable new target with potential utility as a novel treatment for patients with MSI CRC. Citation Format: Jennifer Castro, Matthew H. Daniels, Chuang Lu, David Brennan, Deepali Gotur, Young-Tae Lee, Kevin Knockenhauer, April Case, Jie Wu, Shane M. Buker, Julie Liu, Brian A. Sparling, E. Allen Sickmier, Stephen J. Blakemore, P. Ann Boriack-Sjodin, Kenneth W. Duncan, Scott Ribich, Robert A. Copeland. Targeting DHX9 inhibition as a novel therapeutic modality in microsatellite instable colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1136.
Digital holographic particle image velocimetry: eliminating a sign-ambiguity error and a bias error from the measured particle field displacement (2008)

In a typical digital holographic PIV recording set-up, the reference beam and the object beam propagate towards the recording device along parallel axes. Consequently, in a reconstructed volume, the real image of the recorded particle field and the speckle pattern that originates from the virtual image of the recorded particle field overlap. If the recorded particle field experiences a longitudinal displacement between two recordings and if the two reconstructed complex-amplitude fields are analysed with a 3D correlation analysis, two separate peaks appear in the resulting correlation-coefficient volume. The two peaks are located at opposite longitudinal positions. One peak is related to the displacement of the real image and the other peak is related to the displacement of the speckle pattern that originates from the virtual image. Because both peaks have a comparable height, a sign ambiguity appears in the longitudinal component of the measured particle field displacement. Additionally, the measured longitudinal particle field displacement suffers from a bias error. The sign ambiguity and the bias error can be suppressed by applying a threshold operation to the reconstructed amplitude. The sign ambiguity, characterized by Γ, is suppressed by more than a factor of 60. The dimensionless bias error is reduced by a factor of 5.
In situ modification of delafossite type PdCoO2 bulk single crystal for reversible hydrogen sorption and fast hydrogen evolution (2020)

The observation of extraordinarily high conductivity in delafossite-type PdCoO2 is of great current interest, and there is some evidence that electrons behave like a fluid when flowing in bulk crystals of PdCoO2. Thus, this material is an ideal platform for the study of the electron transfer processes in heterogeneous reactions. Here, we report the use of bulk single crystal PdCoO2 as a promising electrocatalyst for hydrogen evolution reactions (HERs). An overpotential of only 31 mV results in a current density of 10 mA cm^(-2), accompanied by high long-term stability. We have precisely determined that the crystal surface structure is modified after electrochemical activation with the formation of strained Pd nanoclusters in the surface layer. These nanoclusters exhibit reversible hydrogen sorption and desorption, creating more active sites for hydrogen access. The bulk PdCoO2 single crystal with ultra-high conductivity, which acts as a natural substrate for the Pd nanoclusters, provides a high-speed channel for electron transfer