gebhart/patrepeval huggingface dataset:
A randomized, open-label, multicenter, adaptive phase 2/3 study of trastuzumab emtansine (T-DM1) versus a taxane (TAX) in patients (pts) with previously treated HER2-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (LA/MGC/GEJC). (2016)

5 Background: Trastuzumab (H) + capecitabine/fluorouracil + cisplatin is standard of care for 1 st -line HER2-positive MGC/GEJC but there is no established HER2-targeted 2 nd -line regimen. T-DM1 (H linked to DM1) is approved for HER2-positive metastatic breast cancer previously treated with H + TAX (separately or in combination). This and preclinical HER2-positive GC models provided the rationale for GATSBY (NCT01641939). Methods: GATSBY is a 3-arm randomized, adaptive, seamless phase 2/3 global study of T-DM1 vs TAX in pts with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization-positive), unresectable LA/MGC/GEJC who progressed during or after 1 st -line fluoropyrimidine + platinum ± HER2-targeted therapy. Pts were initially randomized 2:2:1 to T-DM1 3.6 mg/kg every 3 weeks (q3w), T-DM1 2.4 mg/kg weekly (qw), or physician’s choice of paclitaxel 80 mg/m 2 qw or docetaxel 75 mg/m 2 q3w. An independent data monitoring committee selected T-DM1 qw for further study and subsequent patients were randomized 2:1 to this or TAX. The primary endpoint is overall survival (OS); all T-DM1 qw data are analyzed, including dose selection. Results: At clinical cutoff, 06/30/15, 415 pts had been randomized overall: 228 to T-DM1 qw, 117 to TAX (70 T-DM1 q3w pts reported separately); 77.4% had prior HER2-targeted therapy; 29.9% prior gastrectomy; 46.1% were Asian. Efficacy/safety are tabulated. Conclusions: T-DM1 2.4 mg/kg qw did not show an efficacy benefit over TAX. Grade ≥3 AE rates were numerically lower with T-DM1 vs TAX and rates of SAEs, fatal AEs, and treatment discontinuations due to AEs were comparable between arms. Clinical trial information: NCT01641939. [Table: see text]
Amazon, Google and Microsoft Solutions for IoT: Architectures and a Performance Comparison (2019)

Internet of Things (IoT) aims to connect the real world made up of devices, sensors and actuators to the virtual world of Internet in order to interconnect devices with each other generating information from the gathered data. Devices, in general, have limited computational power and limited storage capacity. Cloud Computing (CC) has virtually unlimited capacity in terms of storage and computing power, and is based on sharing resources. Therefore, the integration between IoT and CC seems to be one of the most promising solutions. In fact, many of the biggest companies that offer Cloud Services are focusing on the IoT world to offer services also in this direction to their users. In this paper we compare the three main Cloud Platforms (Amazon Web Services, Google Cloud Platform and Microsoft Azure) regarding to the services made available for the IoT. After describing the typical architecture of an IoT application, we map the Cloud-IoT Platforms services with this architecture analyzing the key points for each platform. At the same time, in order to conduct a comparative analysis of performance, we focus on a service made available by all platforms (MQTT middleware) building the reference scenarios and the metrics to be taken into account. Finally, we provide an overview of platform costs based on different loads. The aim is not to declare a winner, but to provide a useful tool to developers to make an informed choice of a platform depending on the use case.
Dichotic pitches as illusions of binaural unmasking. II. The Fourcin pitch and the dichotic repetition pitch (1998)

The predictions of three models are compared with respect to existing experimental data on the perception of the Fourcin pitch (FP) and the dichotic repetition pitch (DRP). Each model generates a central spectrum (CS), which is examined for peaks at frequencies consistent with the perceived pitches. A modified equalization-cancellation (mE-C) model of binaural unmasking [Culling and Summerfield, J. Acoust. Soc. Am. 98, 785–797 (1995)] generates a CS which reflects the degree of interaural decorrelation present in each frequency channel. This model accounts for the perceived frequencies of FPs, but produces no output for DRP stimuli. A restricted equalization-cancellation (rE-C) model [Bilsen and Goldstein, J. Acoust. Soc. Am. 55, 292–296 (1974)] sums the time-varying excitation in corresponding frequency channels, without equalization, to form a CS. A central activity pattern (CAP) model [Raatgever and Bilsen, J. Acoust. Soc. Am. 80, 429–441 (1986)] generates a CS by scanning an interaural cross-correlation matrix across frequency. The rE-C and CAP models yield inaccurate predictions of the perceived frequencies of FPs, but predict the occurrence of the DRP and its correct pitch. The complementary predictions of the mE-C model compared to the rE-C and CAP models, together with the evidence that the FP is clearly audible for the majority of listeners, while the DRP is faintly heard by a minority of listeners, suggest that the mE-C model provides the best available account of the FP, and that the DRP is produced by a separate mechanism.
A Local Region of Interest Imaging Method for Electrical Impedance Tomography with Internal Electrodes (2013)

Electrical Impedance Tomography (EIT) is a very attractive functional imaging method despite the low sensitivity and resolution. The use of internal electrodes with the conventional reconstruction algorithms was not enough to enhance image resolution and accuracy in the region of interest (ROI). We propose a local ROI imaging method with internal electrodes developed from careful analysis of the sensitivity matrix that is designed to reduce the sensitivity of the voxels outside the local region and optimize the sensitivity of the voxel inside the local region. We perform numerical simulations and physical measurements to demonstrate the localized EIT imaging method. In preliminary results with multiple objects we show the benefits of using an internal electrode and the improved resolution due to the local ROI image reconstruction method. The sensitivity is further increased by allowing the surface electrodes to be unevenly spaced with a higher density of surface electrodes near the ROI. Also, we analyse how much the image quality is improved using several performance parameters for comparison. While these have not yet been studied in depth, it convincingly shows an improvement in local sensitivity in images obtained with an internal electrode in comparison to a standard reconstruction method.
Rotating shutters: a mechanical way of flattening Gaussian beam profiles in time average (2000)

A mechanical method of flattening the Gaussian intensity distribution of laser beams in time average is presented. Specially shaped rotating shutters are the key feature of this method, which has been applied to achieve homogeneous submicrometer patterning of macroscopically large samples by laser interference exposure. This method represents a simple yet useful alternative to applying beam broadening or degaussing plates (apodizing filters).
The purification and characterization of 4-hydroxy-3-methoxycinnamic (ferulic) acid esterase from Streptomyces olivochromogenes (1991)

A 4-hydroxy-3-methoxycinnamic acid (ferulic acid) esterase has been purified from the extracellular broth of cultures of Streptomyces olivochromogenes after growth on oat splet xylan. The purification procedure utilizes ion exchange on DEAE-BioGel A, anion exchange on Mono Q, gel filtration and hydrophobic interaction chromatography. The purified enzyme appeared as a single band on SDS-PAGE, with an apparent Mr of 29,000. Two bands, at pI7.9 and 8.5, were observed on isoelectric focusing. With methyl ferulate as substrate, the pH and temperature optima were 5.5 and 30 degrees C respectively, with a Km of 1.86 mM and Vmax of 0.3 mumols min-1 mg-1. The purfied enzyme released ferulic acid from de-starched wheat bran only in the presence of xylanase.
The Heat-Transfer Method: A Versatile Low-Cost, Label-Free, Fast, and User-Friendly Readout Platform for Biosensor Applications (2014)

In recent years, biosensors have become increasingly important in various scientific domains including medicine, biology, and pharmacology, resulting in an increased demand for fast and effective readout techniques. In this Spotlight on Applications, we report on the recently developed heat-transfer method (HTM) and illustrate the use of the technique by zooming in on four established bio(mimetic) sensor applications: (i) mutation analysis in DNA sequences, (ii) cancer cell identification through surface-imprinted polymers, (iii) detection of neurotransmitters with molecularly imprinted polymers, and (iv) phase-transition analysis in lipid vesicle layers. The methodology is based on changes in heat-transfer resistance at a functionalized solid-liquid interface. To this extent, the device applies a temperature gradient over this interface and monitors the temperature underneath and above the functionalized chip in time. The heat-transfer resistance can be obtained by dividing this temperature gradient by the power needed to achieve a programmed temperature. The low-cost, fast, label-free and user-friendly nature of the technology in combination with a high degree of specificity, selectivity, and sensitivity makes HTM a promising sensor technology.
HIGH-SPEED RAILWAYS (1974)

DETAILS ARE GIVEN OF THE STUDY OF THE STABILITY OF THE TGV01 TURBOTRAIN AND OF THE TESTS CARRIED OUT TO SELECT THE ROLLING STOCK WHICH WILL TRAVEL AT 260 KM/H ON THE NEW PARIS-LYON LINE. REASONS ARE GIVEN FOR THE SELECTION OF CATENARY ENERGY SUPPLY RATHER THAN TURBINE ENERGY SUPPLY, AND GRAPHS SHOW A COMPARISON BETWEEN THE ENERGY CONSUMPTION OF THE TURBOTRAIN AND THAT OF OTHER TRANSPORT MODES (AIRCRAFT, CARS, AEROTRAIN). COMMENTS ARE ADDED ON THE EFFECTS OF HIGH SPEED ON GRADIENT AND RADIUS OF CURVATURE OF THE TRACKS.
A Model-Based Approach to Constructing Music Similarity Functions (2006)

Several authors have presented systems that estimate the audio similarity of two pieces of music through the calculation of a distance metric, such as the Euclidean distance, between spectral features calculated from the audio, related to the timbre or pitch of the signal. These features can be augmented with other, temporally or rhythmically based features such as zero-crossing rates, beat histograms, or fluctuation patterns to form a more well-rounded music similarity function. It is our contention that perceptual or cultural labels, such as the genre, style, or emotion of the music, are also very important features in the perception of music. These labels help to define complex regions of similarity within the available feature spaces. We demonstrate a machine-learning-based approach to the construction of a similarity metric, which uses this contextual information to project the calculated features into an intermediate space where a music similarity function that incorporates some of the cultural information may be calculated.
Organic electronics from perylene to organic photovoltaics: painting a brief history with a broad brush (2010)

The past ten years have witnessed the development of bulk-heterojunction (BHJ) solar cells, which have emerged as an attractive renewable energy source in response to rising energy costs and environmental pollution. In such a solar cell, charge transfer at the donor–acceptor interface is a crucial aspect that significantly affects overall device efficiency. Therefore, the choice of these two components and their design are important factors for the optimization of plastic solar cells (PSCs). This feature article correlates the performance of the device to the active layer composites, analyzing the motivations behind specific BHJ designs. Several low-bandgap polymers are described based on their different donor–acceptor units and their influence on both the optical absorption and the electrochemical properties. As for the accepting materials, we examine the effect of chemical functionalization in a series of fullerene derivatives, carbon nanotubes and non-fullerene based compounds on their performances in PSCs. The understanding of film-morphology control is also briefly discussed.
β-Amyloid Peptide Secretion by a Microglial Cell Line Is Induced by β-Amyloid-(25–35) and Lipopolysaccharide (1996)

beta-Amyloid protein (betaAP) deposition is a neuropathologic hallmark of Alzheimer's disease (AD). Yet, the source of cerebral betaAP in AD is controversial. We examined the production of betaAP by the BV-2 immortalized microglial cell line using a sensitive enzyme immunoassay. Constitutive production of betaAP was detected in conditioned media from unstimulated BV-2 cells. Further, production of betaAP was induced by treatment of cultures by lipopolysaccharide (LPS) or betaAP-(25-35) and was inhibited by the calpain protease inhibitor MDL 28170. Treatment of BV-2 cells with LPS or betaAP-(25-35) did not affect cell-associated beta-amyloid precursor protein levels. These findings suggest that microglia may be an important source of betaAP in AD, and that microglial production of betaAP may be augmented by proinflammatory stimuli or by betaAP itself.
Flexible multimedia system architecture with adaptive QoS guarantee functions (2002)

Proposes a flexible multimedia system (FMS) which is based on an agent-oriented architecture. The system is able to organize the required functions itself, and to provide both real-time and stored multimedia information services simultaneously to users, even though various users' multimedia environments and the resource utility of the computers or networks have been dynamically changed. This distributed multimedia system not only integrates various multimedia information distributed over computer networks but it also provides that information to the users in accordance with their requirements during real-time multimedia communication which must guarantee the user-requested quality of service (QoS), even though the computer and network resources may change statically or dynamically. This paper describes the FMS architecture for a multimedia teleconferencing service with adaptive QoS-guarantee functions, and designs the FMS so as to implement a prototype system. In this teleconferencing service, the FMS is able to realize one of the multimedia communication services flexibly for service requests and QoS requests from users.
Optimal bucket algorithms for large MPI collectives on torus interconnects (2010)

Collectives are an important and frequently used component of MPI. Bucket algorithms, also known as "large vector" algorithms, were introduced in the early 90's and have since evolved as a well known paradigm for large MPI collectives. Many modern day supercomputers such as the IBM Blue Gene and Cray XT are based on torus interconnects that offer a highly scalable interconnection architecture for distributed memory systems. While near optimal algorithms have been developed for torus interconnects in other paradigms, such as spanning trees, bucket algorithms have not been optimally extended to these networks. In this paper, we study the basic "divide, distribute and gather" MPI collectives for bucket algorithms -- Allgather, Reduce-scatter and Allreduce -- for large messages on torus interconnects.
Scenario Simulation: Theory and Methodology (1998)

This paper presents a new simulation methodology for quantitative risk analysis of large multi-currency portfolios. The model discretizes the multivariate distribution of market variables into a limited number of scenarios. This results in a high degree of computational efficiency when there are many sources of risk and numerical accuracy dictates a large Monte Carlo sample. Both market and credit risk are incorporated. The model has broad applications in financial risk management, including value at risk. Numerical examples are provided to illustrate some of its practical applications.
Optimized Speech Understanding with the Continuous Interleaved Sampling Speech Coding Strategy in Patients with Cochlear Implants: Effect of Variations in Stimulation Rate and Number of Channels (2000)

The purpose of this study was to investigate the effect of systematic variations in stimulation rate and number of channels on speech understanding in 13 patients with cochlear implants who used the continuous interleaved sampling speech coding strategy. Reducing the stimulation rate from 1,515 to 1,730 pulses per second per channel to 600 pulses per second per channel resulted in decreased overall performance; the understanding of monosyllables and consonants was more affected than the understanding of vowels. Reducing the number of active channels below 7 or 8 channels decreased speech understanding; the identification of vowels and monosyllables was most affected. We conclude that vowel recognition with the continuous interleaved sampling strategy relies on spectral cues more than on temporal cues, increasing with the number of active channels, whereas consonant recognition is more dependent on temporal cues and stimulation rate.
Simultaneous stereoscopic fundus camera incorporating a single optical axis. (1980)

The method of stereoscopic fundus photography, where both photographs are taken simultaneously, yields the most consistent and reproducible record of depths in the fundus. However, all systems devised to date have had undesirable photographic aberrations. For the most part, this has resulted because the optical axis of each image is not the same as that of the objective lens. A single-axis system has now been devised to minimize distortions in the stereoscopic photographs, which therefore makes stereophotogrammetry relatively simple. This design also has other advantages such as simplified alignment procedures, the use of Barlow lenses for multiple magnifications, and various paired apertures for obtaining photographs especially adapted to unusual situations.
A 96 dB SNDR current-mode continuous-time ΔΣ modulator for electrochemical sensor arrays (2015)

A low-voltage fully differential current-mode continuous time delta-sigma modulator is presented for application in electrochemical sensor arrays. Although a first order topology is realized by using a single differential integrator, second order noise shaping is achieved. A differential quantizer based on current controlled oscillators (CCOs) allows a current-mode implementation with high noise-immunity and low-voltage compatibility. Thanks to the differential design nonlinearity impact on circuit performance is kept low. Moreover, the typical clock-jitter sensitivity for continuous time modulators is addressed by a switched shaped-current feedback DAC. The modulator implemented in 180 nm standard CMOS technology consumes 28μW and achieves an SNDR of 95dB at a signal bandwidth of 10 kHz and an oversampling ratio of 256.
Short Laser Pulses ; Optical Applications (1987)

Optical processing of optical signals involves beam interactions through materials : mixing of signals Si and S., by the material non-linear susceptibility may generate new waves S3, of amplitude proportional to the product of the interfering beams amplitudes. Combination of beam multiplications with usual linear beam superposition (addition) achieved by conventional interferometers is the general basis of all-optical operations. Unfortunately optical materials often exhibit very weak non-linear susceptibilities : generation of the S3 component frequently taluirT5 that the product of the interaction length by the intensity of the co-propagating waves lies in the range 10 -10 W.m. It is clearly not possible to work at such levels of continuous laser power. Thus very active research is presently devoted to new highly non-linear materials where wave interactions may occur at moderate c.w. power. But stronger non-linearities appear generally connected with slower responses to field excitations. SHORT LASER PUL-SES, on the subnano- to subpicosecond time scales, offer another effective alternative to high-speed "opto-optical" signal processing : indeed one picosecond pulse ofi5nanojole energy focused onto the Airy disk of minimum area (one squared wavelength) shines the focus by a 10 W.m illumination. Then, despite low pulse energy, the above "interaction product" reaches the threshold of non-linear susceptibilities after transmission through less than one millimeter of conventional optical material. For instance such pulses will be produced at 100 MHz repetition rat! in the "mode-locked" emission of 1.5 m long Laser cavity, with moderate average power (1 W) and linewidth (10 Hz, i.e. 3 nm around 1000 nm average wavelength).
The methyltransferase SMYD3 mediates the recruitment of transcriptional cofactors at the <i>myostatin</i> and <i>c-Met</i> genes and regulates skeletal muscle atrophy (2013)

Elucidating the epigenetic mechanisms underlying muscle mass determination and skeletal muscle wasting holds the potential of identifying molecular pathways that constitute possible drug targets. Here, we report that the methyltransferase SMYD3 modulates myostatin and c-Met transcription in primary skeletal muscle cells and C2C12 myogenic cells. SMYD3 targets the myostatin and c-Met genes and participates in the recruitment of the bromodomain protein BRD4 to their regulatory regions through protein-protein interaction. By recruiting BRD4, SMYD3 favors chromatin engagement of the pause-release factor p-TEFb (positive transcription elongation factor) and elongation of Ser2-phosphorylated RNA polymerase II (PolIISer2P). Reducing SMYD3 decreases myostatin and c-Met transcription, thus protecting from glucocorticoid-induced myotube atrophy. Supporting functional relevance of the SMYD3/BRD4 interaction, BRD4 pharmacological blockade by the small molecule JQ1 prevents dexamethasone-induced myostatin and atrogene up-regulation and spares myotube atrophy. Importantly, in a mouse model of dexamethasone-induced skeletal muscle atrophy, SMYD3 depletion prevents muscle loss and fiber size decrease. These findings reveal a mechanistic link between SMYD3/BRD4-dependent transcriptional regulation, muscle mass determination, and skeletal muscle atrophy and further encourage testing of small molecules targeting specific epigenetic regulators in animal models of muscle wasting.
MST1‐JNK promotes apoptosis via caspase‐dependent and independent pathways (2001)

These results suggest that MST1 most likely promotes two events through JNK activation; first, MST1 induces the activation of caspases, resulting in CAD-mediated DNA fragmentation, and second, MST1 induces chromatin condensation and membrane blebbing without utilizing downstream caspases.
Current and Emerging Therapies for Advanced Adrenocortical Carcinoma (2011)

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with a poor prognosis. Complete surgical resection offers the only potential for cure; however, even after apparently successful excision, local or metastatic recurrence is frequent. Treatment options for advanced ACC are severely limited. Mitotane is the only recognized adrenolytic therapy available; however, response rates are modest and unpredictable whereas systemic toxicities are significant. Reported responses to conventional cytotoxic chemotherapy have also been disappointing, and the rarity of ACC had hampered the ability to undertake randomized clinical studies until the establishment of the First International Randomized Trial in Locally Advanced and Metastatic Adrenocortical Carcinoma. This yet-to-be reported study seeks to identify the most effective first- and second-line cytotoxic regimens. The past decade has also seen increasing research into the molecular pathogenesis of ACCs, with particular interest in the insulin-like growth factor signaling pathway. The widespread development of small molecule tyrosine kinase inhibitors in broader oncological practice is now allowing for the rational selection of targeted therapies to study in ACC. In this review, we discuss the currently available therapeutic options for patients with advanced ACC and detail the molecular rationale behind, and clinical evidence for, novel and emerging therapies.