gebhart/patrepeval huggingface dataset:
Re-activation of HIF signalling pathway in the epicardium improves heart regeneration after myocardial infarction (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background In mouse, cardiac regenerative capacity is maintained for the first week after birth but lost thereafter. Reactivation of this process holds great therapeutic potential, however, the molecular pathways that might be targeted to extend neonatal regeneration remain elusive. Here, we explore a role for hypoxia inducible factor (HIF) family of transcription factors on the regulation of epicardial activity which is essential for cardiac response to injury. Purpose HIF signalling might be involved in the quiescence of the epicardium observed in the first week of life. Thus, HIF stabilisation may induce epicardial re-activation and extend the 7-day regenerative window in a neonate mouse model of myocardial infarction (MI). Methods We analysed epicardial expression of HIF signalling during embryonic development, and in a regenerative post-natal day 1 (P1) versus non-regenerative (P7) mouse model by single cell RNA-sequencing. Next, we established in vitro epicardial explants to confirm the role of HIF signalling in epicardial activation, and finally we induced MI by permanent ligation of the proximal left anterior descending (LAD) coronary artery in P7 mice to test weather HIF signalling re-activation improved heart regeneration in a non-regenerative model. Results Expression of both HIF-1α and HIF-2α is very pronounced at early stages of heart development and gradually decreases throughout gestation. The epicardium preferentially expresses HIF-1α by embryonic day (E) 16.5. Postnatally, GO term analysis showed an enrichment of hypoxia-related pathways in P1 compared to P7 hearts, largely in the epicardial cell population. Accordingly, expression of Phd2, encoding for the main suppressor of HIF signalling, was enriched in P7 derived epicardial cells. Notably, the increase in Phd2 levels coincided with a clear reduction in the expression of Wilms’ tumour 1 (Wt1) in P7 versus P1 hearts, a key player in the epicardial activation. In vitro studies on epicardial explants confirmed regulation of WT1 expression and migration capacity following genetical and pharmacological modulation of HIF signalling. Finally, in vivo targeting of PHD enzymes through pharmacological inhibition with clinically approved drugs in a neonatal mouse model of MI led to prolonged epicardial activation, increased vascularisation, augmented infarct resolution and preserved cardiac function up to 3 weeks after injury. Conclusions Together, these findings show that modulation of HIF signalling can regulate epicardial activity and improve heart regeneration capacity beyond the 7-day regenerative window and may represent a viable therapeutic strategy for treating ischaemic heart disease.
Enhancement of electron-injection detector performance by their unique three-dimensional geometry (2015)

Electron-injection detectors are designed based on a new photon sensing mechanism. Here we demonstrate significant improvements in the device performance as a result of scaling the injector diameter with respect to the trapping/absorbing layer diameter. Devices with an order of magnitude smaller injector area with respect to the trapping/absorbing layer areas show more than an order of magnitude lower dark current, as well as an order of magnitude higher optical gain compared with devices of same size injector and trapping/absorbing layer areas. Devices with 10 &mu;m injector diameter and 30 &mu;m trapping/absorbing layer diameter show an optical gain of ~ 2000 at bias voltage of -3V with a cutoff wavelength of 1700 nm. We also derive analytical expressions for the electroninjection detector optical gain to qualitatively explain the significance of scaling the injector with respect to the absorber.
A multi-DSP implementation of a broad-band adaptive beamformer for use in a hands-free mobile radio telephone (1991)

An implementation of a broadband adaptive array on a multiprocessor digital signal processing system for use in a hands free mobile radio telephone is described. This implementation of a five-microphone adaptive Griffiths-Jim array can handle FIR filters with up to 128 taps behind each microphone at a sampling rate of 8 kHz. The filter structure makes it possible to combine an adaptive array with a noise canceler. The near-field problem has been solved by using focusing, a speech-controlled adaptive algorithm, and a short hourglass. Preliminary measurements indicate a considerable potential for this technique in hands-free mobile telephony. The array gives a 20-30 dB suppression of a broadband jammer covering 300-1100 Hz, even with three reflecting walls surrounding the microphone.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Discovery of MK‐8742: An HCV NS5A Inhibitor with Broad Genotype Activity (2013)

The NS5A protein plays a critical role in the replication of HCV and has been the focus of numerous research efforts over the past few years. NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays, making them attractive components for inclusion in all oral combination regimens. Early work in the NS5A arena led to the discovery of our first clinical candidate, MK-4882 [2-((S)-pyrrolidin-2-yl)-5-(2-(4-(5-((S)-pyrrolidin-2-yl)-1H-imidazol-2-yl)phenyl)benzofuran-5-yl)-1H-imidazole]. While preclinical proof-of-concept studies in HCV-infected chimpanzees harboring chronic genotype 1 infections resulted in significant decreases in viral load after both single- and multiple-dose treatments, viral breakthrough proved to be a concern, thus necessitating the development of compounds with increased potency against a number of genotypes and NS5A resistance mutations. Modification of the MK-4882 core scaffold by introduction of a cyclic constraint afforded a series of tetracyclic inhibitors, which showed improved virologic profiles. Herein we describe the research efforts that led to the discovery of MK-8742, a tetracyclic indole-based NS5A inhibitor, which is currently in phase 2b clinical trials as part of an all-oral, interferon-free regimen for the treatment of HCV infection.
Sensor-Network-Aided Cognitive Radio: On the Optimal Receiver for Estimate-and-Forward Protocols Applied to the Relay Channel (2007)

Cognitive radio describes a promising concept for improving the utilization of radio spectrum. It allows secondary users to access licensed radio spectrum in an opportunistic fashion, given that the quality of service for primary users is maintained. In this scenario, the detection of unused radio spectrum is the main obstacle: it requires the recognition of low- power signals in a noisy environment. Therefore, we consider the case where cognitive users are supported by a wireless sensor network (WSN) providing beliefs on the event that the primary user is active. The beliefs provided by the WSN nodes are then combined by the cognitive radio in order to make a final decision. Due to limitations in complexity, power, and bandwidth, the WSN nodes apply the estimate-and-forward protocol to communicate their beliefs and to relay the beliefs of adjacent nodes. For the case where the WSN is subject to noisy communication links, we derive and analyze the optimal receiver which provides the cognitive radio with log-likelihood ratios for the estimated and forwarded hypotheses. The performance of the optimal receiver is compared to the performance of sub-optimal receivers.
Star-to-Bottlebrush Transition in Extensional and Shear Deformation of Unentangled Polymer Melts (2023)

A series of model poly((±)-lactide) (PLA) graft copolymers was synthesized by ring-opening metathesis polymerization and used to probe the star-to-bottlebrush transition in shear and extensional flows. Ten samples with backbone degrees of polymerization 11 ≤ Nbb ≤ 420 were investigated using small-amplitude oscillatory shear (SAOS) and extensional rheometry measurements. Each contained one PLA side chain of length Nsc = 72 per two backbone repeating units on average (graft density of z = 0.5). The star-like to bottlebrush transition was identified at Nbb = 50–69 using SAOS. In extension, melt strain hardening is absent in the star-like melts (Nbb ≤ 50) but is prominent in the bottlebrush limit (Nbb > 69). The onset of melt strain hardening occurs at a time scale equivalent to the Rouse time of the backbone. A molecular interpretation of these results builds upon recent conjectures related to strain-induced increases in interchain friction in bottlebrush polymers. These findings will be useful in designing bottlebrush melts that strain harden, which is critical in various types of processing methods involving extensional flows, including foaming, 3D printing, and film-blowing.
Time-of-Flight Electron Energy Loss Spectroscopy by Longitudinal Phase Space Manipulation with Microwave Cavities (2017)

The possibility to perform high-resolution time-resolved electron energy loss spectroscopy has the potential to impact a broad range of research fields. Resolving small energy losses with ultrashort electron pulses, however, is an enormous challenge due to the low average brightness of a pulsed beam. In this letter, we propose to use time-of-flight measurements combined with longitudinal phase space manipulation using resonant microwave cavities. This allows for both an accurate detection of energy losses with a high current throughput, and efficient monochromation. First, a proof-of-principle experiment is presented, showing that with the incorporation of a compression cavity the flight time resolution can be improved significantly. Then, it is shown through simulations that by adding a cavity-based monochromation technique, a full-width-at-half-maximum energy resolution of 22 meV can be achieved with 3.1 ps pulses at a beam energy of 30 keV with currently available technology. By combining state-of-the-art energy resolutions with a pulsed electron beam, the technique proposed here opens up the way to detecting short-lived excitations within the regime of highly collective physics.
Polymer gate dielectric pentacene TFTs and circuits on flexible substrates (2003)

We have fabricated organic thin film transistors (TFTs) and integrated circuits on flexible polymeric substrates with solution-processed polymer gate dielectric layers and obtained transistors with excellent electrical characteristics, as well as 5-stage ring oscillators with signal propagation delay as low as 22 /spl mu/sec per stage. To our knowledge, these are the fastest integrated circuits with organic transistors on flexible substrates reported to date.
Downlink Resource Allocation for Next Generation Wireless Networks with Inter-Cell Interference (2013)

This paper presents a novel downlink resource allocation scheme for OFDMA-based next generation wireless networks subject to inter-cell interference (ICI). The scheme consists of radio resource and power allocations, which are implemented separately. Low-complexity heuristic algorithms are first proposed to achieve the radio resource allocation, where graph-based framework and fine physical resource block (PRB) assignment are performed to mitigate major ICI and hence improve the network performance. Given the solution of radio resource allocation, a novel distributed power allocation is then performed to optimize the performance of cell-edge users under the condition that desirable performance for cell-center users must be maintained. The power optimization is formulated as an iterative barrier-constrained water-filling problem and solved by using the Lagrange method. Simulation results indicate that our proposed scheme can achieve significantly balanced performance improvement between cell-edge and cell-center users in multi-cell networks compared with other schemes, and therefore realize the goal of future wireless networks in terms of providing high performance to anyone from anywhere.
Inside Back Cover: Detection of Individual Vapors and Their Mixtures Using a Selectivity‐Tunable Three‐Dimensional Network of Plasmonic Nanoparticles (Angew. Chem. Int. Ed. 39/2013) (2013)

Detection selectivity remains the key challenge for the development of vapor sensors that limits their applications in complex environments. In their Communication on page 10360 ff., R. A. Potyrailo et al. describe the detection of individual vapors and their mixtures by using only a single sensing film formed from a three-dimensional network of plasmonic nanoparticles. The tunable selectivity is achieved within a single multivariable sensor.
The phospholipase A2 inhibitor methyl indoxam suppresses diet‐induced obesity and glucose intolerance in mice (2009)

These results show that oral supplementation of a diabetogenic diet with the Pla2g1b inhibitor methyl indoxam effectively suppresses diet-induced obesity and diabetes in mice. This suggests that Pla2g1b inhibition may be a potentially effective oral therapeutic option for treatment of obesity and diabetes.
Negative-tone resist for phase-shifting mask technology: a progress report (2000)

With the objective to make smaller device structures at a given illumination wavelength the semiconductor industry is more and more trying to implement Phase-Shifting Masks (PSMs) as resolution enhancement technique for DUV lithography. However, with positive photoresists there is a phase edge problem. Using negative resists is the easiest approach to solve the phase edge problem. This is one of the reasons why negative resists are becoming more and more attractive for leading edge lithography. Therefore, we are developing a novel negative resist with 248/193 nm crossover capability. Most experiments were done in imitation of the CARL<SUP>R</SUP> bilayer resist process. The goal was to use established resist techniques and polymer materials, and just to change the generators and additives to get tone reversal. Using a photoacid generator (PAG) as additive leads to positive tone. In contrary with a photobase generator (PBG) and thermoacid generator (TAG) combination in a negative tone behavior is observed. Comprehensively, this blending concept allows the use of similar working polymers in both, positive and negative resists. The generator efficiencies were studied as well as the diffusion behavior of resist components during resist processing. Especially, process factors like baking conditions were investigated with the objective to control diffusion and limit resist outgassing in a high activation energy resist platform. Furthermore, in adaptation of the CARL<SUP>R</SUP> process, a separate liquid silylation step was integrated and investigated for various process conditions. In our paper we will discuss the characteristics and the lithographic capabilities of the novel methacrylate based negative resists. First promising results are based on DUV (248/193 nm) and ebeam exposures. Recent results with our positive version indicate the same outstanding possibilities. We expect a similar performance for the negative pendant in the near future.
Lithographic Performance of Extreme Ultravolet Full-Field Exposure Tool at Selete (2009)

The Selete full-field etreme ultraviolet (EUV) exposure tool, the EUV1, was manufactured by Nikon and is being developed at Selete. Its lithographic performance was evaluated in exposure experiments with a static slit using line and space (L&S) patterns, Selete Standard Resist 03 (SSR3), a numerical aperture (NA) of 0.25, and conventional illumination (σ= 0.8). The results showed that 25 nm L&S patterns were resolved. Dynamic exposure experiments showed the resolution to be 45 nm across the exposure field and the critical dimension (CD) uniformity across a shot to be 7 nm, which is sufficient for an alpha-level lithography tool.
Parametric Response Mapping as an Imaging Biomarker in Lung Transplant Recipients (2016)

PRM is a novel imaging tool for lung transplant recipients presenting with spirometric decline. Quantifying underlying small airway obstruction via PRM<sup>fSAD</sup> helps further stratify the risk of death in patients with diverse spirometric decline patterns.
Replication-Selective Oncolytic Adenoviruses (2004)

Replication-selective oncolytic viruses are being developed as novel, targeted anticancer agents (virotherapy) (1,2). Viruses have evolved to infect cells, replicate, induce cell death, release viral particles, and, finally, to spread in human tissues. Replication in tumor tissue leads to amplification of the input dose at the tumor site, whereas a lack of replication in normal tissues can result in efficient clearance and reduced toxicity. Revolutionary advances in molecular biology and genetics have led to a fundamental understanding of both the replication and pathogenicity of viruses and carcinogenesis. These advances have allowed novel agents to be engineered to enhance their safety and/or their antitumoral potency (2,3). One approach to engineering adenovirus selectivity has been to complement loss-of-function mutations in cancers with loss-of-function mutations within the adenovirus genome. Many of the same critical regulatory proteins that are inactivated by viral gene products during adenovirus replication are also inactivated during carcinogenesis (4–7). Because of this convergence, the deletion of viral genes that inactivate these cellular regulatory proteins can be complemented by genetic inactivation of these proteins within cancer cells (8,9). This concept was proven by the E1B55kD deletion in the dl1520 mutant virus (Onyx-015), which is selective for cells lacking functional p53 (8) enabling viral replication in the majority of human cancers. Clinical trials with dl1520 ultimately proved the selectivity and relative safety of this approach (i.e., refs. 10–12). However, more efficacious adenoviruses are needed.
Supplemental Figure 5 from AGS16F Is a Novel Antibody Drug Conjugate Directed against ENPP3 for the Treatment of Renal Cell Carcinoma (2023)

&lt;p&gt;Supplemental Figure 5. Immunostaining for cleaved PARP-1 and PPH3 in tumors.&lt;/p&gt;
Identification of deubiquitinase inhibitors via high-throughput screening using a fluorogenic ubiquitin-rhodamine assay (2021)

Identification of selective deubiquitinase (DUB) inhibitors is critical for probe development to further understand and explore DUB biological function. Here, we detail the optimization and deployment of an <i>in vitro</i> fluorogenic ubiquitin-rhodamine assay to conduct high-throughput screening of a small molecule library against a panel of DUBs. In screening the compound library against multiple DUBs in parallel, we describe an approach for identifying selective DUB inhibitors and provide a roadmap for enabling selective DUB inhibitor discovery. For complete details on the use and execution of this protocol, please refer to Varca et al. (2021).
Genetic polymorphisms to predict progression-free survival in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone therapy: Results from the NCI 9012 trial. (2017)

145 Background: Abiraterone is a CYP17 inhibitor approved for treatment of men with mCRPC. The NCI 9012 trial evaluated abiraterone alone with or without the PARP inhibitor veliparib in mCRPC patients. We hypothesized that germline genetic variation in the androgen axis and other metabolic enzymes would predict response to veliparib + abiraterone vs. abiraterone alone. Methods: A randomized trial cohort of (148) men with advanced mCRPC treated with abiraterone with or without veliparib was genotyped for 120 DNA polymorphisms in genes involved in androgen metabolism using Lifetech Open array chips. Blood for pharmacogenomic SNP analysis were collected at pre-treatment from each subject into 10-mL EDTA tube. Polymorphisms were tested using Cox models without treatment for prognostic testing and with treatment arm for predictive testing. Results: Genotyping was completed in 143 of 148 men; all were treated with abiraterone; 72 without veliparib (Median PFS: 10.3m) and 71 with veliparib (Median PFS: 11.3m). Polymorphisms in separate genes (SLCO2B1, KIF3C CYP19A, ESR1) were significantly (P ≤ .025) associated with progression-free survival (PFS) during abiraterone (q-value &lt; 0.69). Polymorphisms in (CYP11A1, HSD17B4, ABHD13;LIG4, CYP19A1, HSD17B4, TRMT11) were predictive for PFS in patients treated with combination of abiraterone/veliparib compared to abiraterone alone (p-value &lt; 0.025; q-value &lt; 0.28). Conclusions: This analysis examines the influence of inherited variations on the efficacy of abiraterone, establishing the importance of pharmacogenomics on individual’s response to this therapy. Genotyping patients at these loci could be predictive of improved PFS to valiparib in combination with abiraterone. Further analysis of the association of more than one polymorphisms compared to zero or one with PFS associated with improved TTP demonstrated a better response to therapy than individuals carrying zero or one is ongoing. Clinical trial information: NCT01576172.
Noncontact fluorescence diffuse optical tomography of heterogeneous media (2007)

Fluorescence-enhanced diffuse optical tomography is expected to be useful to the collection of functional information from small animal models. This technique is currently limited by the extent of tissue heterogeneity and management of the shape of the animals. We propose an approach based on the reconstruction of object heterogeneity, which provides an original solution to the two problems. Three evaluation campaigns are described: the first two were performed on phantoms designed to test the reconstructions in highly heterogeneous media and noncontact geometries; the third was conducted on mice with lung tumors to test fluorescence yield reconstruction feasibility in vivo.
O2 as initiator of autocatalytic degradation of hemicelluloses and monosaccharides in hydrothermal treatment of spruce (2022)

The influence of oxygen (0-50 bar) on the molar mass and composition of hemicelluloses after hydrothermal treatment of spruce chips was studied in a batch reactor setup at 130 °C-160 °C. Purified galactoglucomannan was studied as a reference. The dissolved oxygen enhanced significantly the depolymerization of hemicelluloses from over 15,000 g/mol to 180 g/mol (monomers) as well as promoted acids formation from the monosaccharides. About 2-3 times faster depolymerization was observed already with rather low amounts of oxygen (2-8 bar), while the kinetics of depolymerization was significantly slower in inert atmosphere. The decrease in pH from neutral to as low as 2.5 lead to an autocatalytic effect on the polysaccharide hydrolysis and the consecutive reactions of monosaccharides. The results emphasize the importance of performing hydrothermal treatment under inert atmosphere if large polymeric hemicellulsoses are desired or if monosaccharides are targeted in hydrolysis of hemicelluloses. If autocatalysis begins, it is difficult to stop.
Hardware-corroborated Variability-Aware SRAM Methodology (2013)

The paper presents a novel hardware-measurement based methodology to extract within-product-array variability as opposed to kerf. The methodology was applied to a 45nm 2.4Mb SRAM design with emphasis on critical dimension measurements. Local mismatch and spatial variations, LER effects and backend effects were measured. Lithographic models were tuned to the 45nm process. Statistically measured variability in critical process units along with extracted long-range CD variation through lithography simulations were then fed to a newly developed statistical engine to predict design yield, leakage and performance. The predicted yield results were then corroborated with the hardware providing feedback for process tuning. In addition to monitoring mature processes, such hardware measurement techniques can also be used to monitor or decipher yield-detractor defects.