gebhart/patrepeval huggingface dataset:
Novel regulators of PrPC biosynthesis revealed by genome-wide RNA interference (2021)

The cellular prion protein PrPC is necessary for prion replication, and its reduction greatly increases life expectancy in animal models of prion infection. Hence the factors controlling the levels of PrPC may represent therapeutic targets against human prion diseases. Here we performed an arrayed whole-transcriptome RNA interference screen to identify modulators of PrPC expression. We cultured human U251-MG glioblastoma cells in the presence of 64'752 unique siRNAs targeting 21'584 annotated human genes, and measured PrPC using a one-pot fluorescence-resonance energy transfer immunoassay in 51'128 individual microplate wells. This screen yielded 743 candidate regulators of PrPC. When downregulated, 563 of these candidates reduced and 180 enhanced PrPC expression. Recursive candidate attrition through multiple secondary screens yielded 54 novel regulators of PrPC, 9 of which were confirmed by CRISPR interference as robust regulators of PrPC biosynthesis and degradation. The phenotypes of 6 of the 9 candidates were inverted in response to transcriptional activation using CRISPRa. The RNA-binding post-transcriptional repressor Pumilio-1 was identified as a potent limiter of PrPC expression through the degradation of PRNP mRNA. Because of its hypothesis-free design, this comprehensive genetic-perturbation screen delivers an unbiased landscape of the genes regulating PrPC levels in cells, most of which were unanticipated, and some of which may be amenable to pharmacological targeting in the context of antiprion therapies.
Creativity and mental disorder: Family study of 300 000 people with severe mental disorder (2011)

A familial cosegregation of both schizophrenia and bipolar disorder with creativity is suggested.
Trial watch: Peptide-based vaccines in anticancer therapy (2018)

Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.<b>Abbreviations:</b> CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen.
EDNS0 Option for Indicating AAAA Record Synthesis and Format (2011)

Advanced hosts and applications benefit of the knowledge of an IPv6
address, AAAA record, synthesis taking place in the network. This
draft proposes new ENDS0 option for communicating the synthesis is
taking place, used address format, and the IPv6 prefix and suffix used
by the DNS64. The communicated information enables hosts to perform
local IPv6 address synthesis.
Discovery, Development, and Commercialization of Gold Catalysts for Acetylene Hydrochlorination (2015)

Vinyl chloride monomer (VCM) is a major chemical intermediate for the manufacture of polyvinyl chloride (PVC), which is the third most important polymer in use today. Hydrochlorination of acetylene is a major route for the production of vinyl chloride, since production of the monomer is based in regions of the world where coal is abundant. Until now, mercuric chloride supported on carbon is used as the catalyst in the commercial process, and this exhibits severe problems associated with catalyst lifetime and mercury loss. It has been known for over 30 years that gold is a superior catalyst, but it is only now that it is being commercialized. In this Perspective we discuss the use and disadvantages of the mercury catalyst and the advent of the gold catalysts for this important reaction. The nature of the active site and the possible reaction mechanism are discussed. Recent advances in the design and preparation of active gold catalysts containing ultralow levels of gold are described. In the final part, a view to the future of this chemistry will be discussed as well as the possible avenues for the commercial potential of gold catalysis.
A new reference genome sequence for genotyping virulence in continental European field populations of Globodera pallida (2018)

Plant-parasitic nematodes form an increasingly important problem in agriculture, causing significant crop losses worldwide. The majority of these losses are caused by a small number of species, such as cyst nematodes (e.g., Globodera rostochiensis and G. pallida), root-knot nematodes (Meloidogyne spp.) and stem nematodes (Ditylenchus spp.). With a regulatory ban on most nematicidal agrochemicals, the main method of control at the moment is the use of resistant crop cultivars. However, the current spectrum of nematode resistance genes used in major crops is extremely narrow. Prolonged exposure of field populations to a narrow range of resistance genes can result in the appearance of nematode genotypes with modified virulence characteristics.To better understand the genetic mechanisms underlying selection for virulence in the potato cyst nematode G. pallida in the Netherlands, we needed to generate a new reference genome. For this, we deliberately chose an old isolate; a population that had not been exposed to potato cultivars harbouring the resistance genes that were most widely used over the past thirty years. We generated a new genome sequence of this G. pallida isolate with PacBio sequencing technology. This resulted in a new genome sequence which consists of significantly fewer and longer contigs than the publicly available genome sequence of this species. An automated procedure was used to create an initial annotation. After a further manual refinement of the annotation with a particular focus on effector families, this genome sequence will serve as a reference for the elucidation of virulence characteristics in G. pallida populations from The Netherlands and surrounding countries.
Amine‐Catalyzed Asymmetric Epoxidation of α,β‐Unsaturated Aldehydes. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
An International Collaborative Standardizing Patient-Centered Outcome Measures in Pediatric Facial Palsy (2019)

NA.
Resource Allocation via Sum-Rate Maximization in the Uplink of Multi-Cell OFDMA Networks (2010)

In this paper, we consider maximizing the sum-rate in the uplink of a multi-cell OFDMA network. The problem has a non-convex combinatorial structure and is known to be NP hard. Due to the inherent complexity of implementing the optimal solution, firstly, we derive an upper and lower bound to the optimal average network throughput. Moreover, we investigate the performance of a near optimal single cell resource allocation scheme in the presence of ICI which leads to another easily computable lower bound. We then develop a centralized sub-optimal scheme that is composed of a geometric programming based power control phase in conjunction with an iterative subcarrier allocation phase. Although, the scheme is computationally complex, it provides an effective benchmark for low complexity schemes even without the power control phase. Finally, we propose less complex centralized and distributed schemes that are well-suited for practical scenarios. The computational complexity of all schemes is analyzed and performance is compared through simulations. Simulation results demonstrate that the proposed low complexity schemes can achieve comparable performance to the centralized sub-optimal scheme in various scenarios. Moreover, comparisons with the upper and lower bounds provide insight on the performance gap between the proposed schemes and the optimal solution.
Effect of Oral Losartan on Orthobiologics: Implications for Platelet-Rich Plasma and Bone Marrow Concentrate—A Rabbit Study (2020)

Recent efforts have focused on customizing orthobiologics, such as platelet-rich plasma (PRP) and bone marrow concentrate (BMC), to improve tissue repair. We hypothesized that oral losartan (a TGF-β1 blocker with anti-fibrotic properties) could decrease TGF-β1 levels in leukocyte-poor PRP (LP-PRP) and fibrocytes in BMC. Ten rabbits were randomized into two groups (N = 5/group): osteochondral defect + microfracture (control, group 1) and osteochondral defect + microfracture + losartan (losartan, group 2). For group 2, a dose of 10mg/kg/day of losartan was administrated orally for 12 weeks post-operatively. After 12 weeks, whole blood (WB) and bone marrow aspirate (BMA) samples were collected to process LP-PRP and BMC. TGF-β1 concentrations were measured in WB and LP-PRP with multiplex immunoassay. BMC cell populations were analyzed by flow cytometry with CD31, CD44, CD45, CD34, CD146 and CD90 antibodies. There was no significant difference in TGF-β1 levels between the losartan and control group in WB or LP-PRP. In BMC, the percentage of CD31+ cells (endothelial cells) in the losartan group was significantly higher than the control group (<i>p</i> = 0.008), while the percentage of CD45+ cells (hematopoietic cells-fibrocytes) in the losartan group was significantly lower than the control group (<i>p</i> = 0.03).
Beta Spectrum ofC14 (1955)

A uniform thin source enriched with ${\mathrm{C}}^{14}$ was formed by vacuum evaporation of metallic lithium which was subsequently exposed to water vapor and carbon dioxide. The Kurie plot shows no deviation from linearity above 7 kev. The maximum energy of the beta spectrum was found to be 158.5\ifmmode\pm\else\textpm\fi{}0.5 kev.
Dispersion-free continuum two-dimensional electronic spectrometer (2014)

Electronic dynamics span broad energy scales with ultrafast time constants in the condensed phase. Two-dimensional (2D) electronic spectroscopy permits the study of these dynamics with simultaneous resolution in both frequency and time. In practice, this technique is sensitive to changes in nonlinear dispersion in the laser pulses as time delays are varied during the experiment. We have developed a 2D spectrometer that uses broadband continuum generated in argon as the light source. Using this visible light in phase-sensitive optical experiments presents new challenges in implementation. We demonstrate all-reflective interferometric delays using angled stages. Upon selecting an ~180 nm window of the available bandwidth at ~10 fs compression, we probe the nonlinear response of broadly absorbing CdSe quantum dots and electronic transitions of Chlorophyll a.
Host-Free Deep-Blue Organic Light-Emitting Transistors Based on a Novel Fluorescent Emitter (2020)

Organic light-emitting transistors (OLETs), with the capability of simultaneously functioning as a light-emitting stack and a thin-film transistor, have received considerable attention for potential applications in active-matrix flat-panel displays. Here, we demonstrate host-free deep-blue OLETs based on a novel small-molecule fluorescent emitter, 10,10'-bis(4-(1-phenyl-1H-benzo[<i>d</i>]imidazol-2-yl)phenyl)-10H,10'H-9,9'-spirobi[acridine] (SPA-PBI), and a high-k dielectric, cross-linked poly(vinyl alcohol) (PVA) polymer. The deep-blue OLETs based on 2,2',2″-(1,3,5-benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) (TPBi) as an electron-transport layer showed an extraordinarily high hole mobility of 4.6 cm<sup>2</sup> V<sup>-1</sup> s<sup>-1</sup>, a brightness of 570 cd m<sup>-2</sup> under a low gate and source-drain voltages of -24 V, and an external quantum efficiency (EQE) of 0.87% at 100 cd m<sup>-2</sup>. Besides, an electroluminescence peak was observed to be at 432 nm and the corresponding CIE coordinates were as deep as (0.16, 0.08). By replacing TPBi with TmPyPB as the electron-transport layer (ETL), the electron transport and hole blocking capability were greatly improved, which led to ∼60% enhancement of the EQE (1.39% at 100 cd m<sup>-2</sup>). These results suggest that using a highly twisted double-donor-acceptor emitter with rationally optimized charge injection could lead to highly efficient deep-blue OLETs.
Deleted DOI: Postfiltering Using Multichannel Spectral Estimation in Multispeaker Environments (2007)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Evaluation of load sharing in HARTS with consideration of its communication activities (1996)

We rigorously analyze load sharing (LS) in a distributed real-time system, called HARTS (Hexagonal Architecture for Real-Time Systems), while considering LS-related communication activities, such as task transfers and state-change broadcasts. First, we give an overview of the general distributed real-time LS approach described previously, and then adapt it to HARTS by exploiting the topological properties of HARTS. Second, we model task arrival/completion/transfer activities in HARTS as a continuous-time Markov chain from which we derive the distribution of queue length and the rate of generating LS-related traffic-task transfer-out rate and state-region change broadcast rate. Third, we derive the distribution of packet delivery time as a function of LS-related traffic rates by characterizing the hexagonal mesh topology and the virtual cut-through capability of HARTS. Finally, we derive the distribution of task waiting time (the time a task is queued for execution plus the time it would spend if the task is to be transferred), from which the probability of a task failing to complete in time, called the probability of dynamic failure, can be computed. The results obtained from our analytic models are verified through event-driven simulations, and can be used to study the effects of varying various design parameters on the performance of LS while considering the details of LS-related communication activities.
Supplementary Movie 1 from Ovarian Cancer Spheroids Use Myosin-Generated Force to Clear the Mesothelium (2023)

&lt;p&gt;File Type: .mov; File Size: 1 MB.&lt;/p&gt;
Xampling: compressed sensing of analog signals (2012)

Xampling generalizes compressed sensing (CS) to reduced-rate sampling of analog signals. A unified framework is introduced for low rate sampling and processing of signals lying in a union of subspaces. Xampling consists of two main blocks: Analog compression that narrows down the input bandwidth prior to sampling with commercial devices followed by a nonlinear algorithm that detects the input subspace prior to conventional signal processing. A variety of analog CS applications are reviewed within the unified Xampling framework including a general filter-bank scheme for sparse shift-invariant spaces, periodic nonuniform sampling and modulated wideband conversion for multiband communications with unknown carrier frequencies, acquisition techniques for finite rate of innovation signals with applications to medical and radar imaging, and random demodulation of sparse harmonic tones. A hardware-oriented viewpoint is advocated throughout, addressing practical constraints and exemplifying hardware realizations where relevant. It will appear as a chapter in a book on "Compressed Sensing: Theory and Applications" edited by Yonina Eldar and Gitta Kutyniok.
Design and Synthesis of Novel Glycopolythiophene Assemblies for Colorimetric Detection of Influenza Virus and E. coli (2000)

A novel family of glycopolythiophenes containing sialic acid or mannose ligands were prepared and evaluated for their ability to bind lectins, virus, and bacteria. For the set of glycopolythiophenes studied, the spacer-length between the polymer backbone and the ligand was varied to optimize binding interactions. The glycopolymers were blue-shifted (absorbance of ca. 400 nm) relative to the corresponding homo-polythiophenes (absorbance ca. 440 nm), suggesting a twisted conformation for the glycopolymers. The altered conformation is likely due to electrostatic or H-bonding interactions between the polymer chains, arising from the carbohydrate ligand. Further conformational changes in the polythiophene backbone were detected by the binding of specific receptors; lectins (wheat germ agglutinin, concanavalin A), Influenza virus, and Escherichia coli. The binding interactions result in an unusual red-shift in the visible absorption of the polymer backbone, suggesting a lengthening of the effective conjugated length upon interaction of the ligand with its congnate receptor. These conjugated glycopolymeric systems offer a potentially new platform for the detection of molecular binding interactions.
Gene and drug delivery using ultrasound-targeted microbubble cavitation (2023)

Therapeutic delivery of oligonucleotides, such as RNAs, has the potential to treat heretofore “undruggable” targets in diseases such as cancer. However, systemic intravascular delivery of RNAs to tumor tissue is limited by the vascular endothelium, which provides a barrier to transendothelial passage of large, charged molecules. To address RNA delivery challenges, we and others have developed an approach employing ultrasound targeted microbubble cavitation (UTMC), which utilizes 2–4 μm diameter gas-filled microbubbles that carry RNA on the shell and also serve as an ultrasound imaging agent. As intravenously injected microbubbles travel through the microcirculation, localized ultrasound induces microbubble cavitation, causing localized payload release from the microbubble. In addition to delivering the RNA payload, UTMC increases endothelial permeability, thus increasing local extravasation of the payload, while sparing non-insonified tissue (reduced off-target effects). Microbubbles are non-immunogenic and protect loaded RNA against nuclease digestion. Because UTMC concentrates the RNA at the tumor site, lower systemic RNA doses can be used, resulting in fewer off-target effects. A unique feature is that the microbubble that carries and releases the RNA also permits simultaneous US imaging of microbubble location. This lecture will review these unique features of UTMC for drug delivery and current work in this area.
The Added Value of Statistical Modeling of Backscatter Properties in the Management of Breast Lesions at US (2014)

The statistical model performs well in the classification of solid breast lesions at US, with the potential of preventing one in four biopsies without missing any malignancy.
Hardware and Physical Layer Adaptation for a Power Constrained MIMO OFDM System (2011)

We propose an approach for minimizing the total power consumed by a multiple-input multiple-output (MIMO) orthogonal frequency division multiplexing communication system. The system under consideration supports a wide range of communication scenarios over a flat fading channel. A communication scenario is defined by throughput requirement, transmission distance, and maximum packet error rate (PER) constraints. Power consumption minimization is achieved by the joint configuration of hardware and physical layer system parameters according to the communication scenario. The configurable parameters are the modulation and coding scheme, antenna configuration, operating bandwidth, power amplifier back-off, analog-to-digital converter resolution, phase-locked loop phase noise power, transmission power, and transmit duty cycle. The optimal parameter configuration is found through a brute-force search over a simulation-based database linking performance with power consumption. Results show that power consumption can be reduced by a factor of 24.6 for a single-input single-output system and 3.79 for a MIMO system at a PER of 10%.
High-q evanescent-mode filters using silicon micromachining and polymer stereolithography (sl) processing (2004)

Evanescent-mode filters are realized by both silicon micromachining as well as layer-by-layer polymer stereolithography (SL) processing. Capacitive loading an enclosed resonator reduces the size of a distributed cavity to be much smaller than a wavelength but which has much higher unloaded Q than lumped elements. The loaded resonators are extended into reduced-size filters with a low insertion loss due to the relatively high quality factor. Size reduction of resonators and filters can be a full order of magnitude depending on the height of the capacitive post. A 14 GHz resonator micro-machined in silicon with 5 mm/spl times/5 mm/spl times/0.45 mm volume reduces the size by 76.8%. The polymer-based fabrication was used to create a resonator with a Q greater than 1,050. An insertion loss of 0.83 dB was measured in a 1.69% filter with a size reduction of 47%. Furthermore, the proposed filters are quasi-planar and capable of integration with other RF components.
Discovery of the Selective Androgen Receptor Modulator MK-0773 Using a Rational Development Strategy Based on Differential Transcriptional Requirements for Androgenic Anabolism Versus Reproductive Physiology (2010)

Selective androgen receptor modulators (SARMs) are androgen receptor (AR) ligands that induce anabolism while having reduced effects in reproductive tissues. In various experimental contexts SARMs fully activate, partially activate, or even antagonize the AR, but how these complex activities translate into tissue selectivity is not known. Here, we probed receptor function using >1000 synthetic AR ligands. These compounds produced a spectrum of activities in each assay ranging from 0 to 100% of maximal response. By testing different classes of compounds in ovariectomized rats, we established that ligands that transactivated a model promoter 40-80% of an agonist, recruited the coactivator GRIP-1 <15%, and stabilized the N-/C-terminal interdomain interaction <7% induced bone formation with reduced effects in the uterus and in sebaceous glands. Using these criteria, multiple SARMs were synthesized including MK-0773, a 4-aza-steroid that exhibited tissue selectivity in humans. Thus, AR activated to moderate levels due to reduced cofactor recruitment, and N-/C-terminal interactions produce a fully anabolic response, whereas more complete receptor activation is required for reproductive effects. This bimodal activation provides a molecular basis for the development of SARMs.
Motexafin gadolinium: a novel radiosensitizer for brain tumors (2009)

For a variety of reasons, the management of brain tumors, both primary and metastatic, remains a considerable challenge. As most systemic therapies do not cross the BBB at therapeutic doses, radiation and surgery have played primary roles in the management of these diseases. Despite significant advances in surgical techniques and radiation delivery, outcomes for most adult brain tumors continue to be poor. In an effort to enhance the effects of radiation in the brain, a variety of radiation sensitizers, including motexafin gadolinium, have been investigated. In the following manuscript, we summarize motexafin gadolinium and its role in brain tumors.