gebhart/patrepeval huggingface dataset:
Pharmacodynamic and Antitumor Activity of BI 836880, a Dual Vascular Endothelial Growth Factor and Angiopoietin 2 Inhibitor, Alone and Combined with Programmed Cell Death Protein-1 Inhibition (2022)

Vascular endothelial growth factor (VEGF) and angiopoietin (ANG)-2 have complementary roles in angiogenesis and promote an immunosuppressive tumor microenvironment. It is anticipated that the combination of VEGF and ANG2 blockade could provide superior activity to the blockade of either pathway alone and that the addition of VEGF/ANG2 inhibition to an anti-programmed cell death protein-1 (PD-1) antibody could change the tumor microenvironment to support T-cell-mediated tumor cytotoxicity. Here, we describe the pharmacologic and antitumor activity of BI 836880, a humanized bispecific nanobody comprising two single-variable domains blocking VEGF and ANG2, and an additional module for half-life extension in vivo. BI 836880 demonstrated high affinity and selectivity for human VEGF-A and ANG2, resulting in inhibition of the downstream signaling of VEGF/ANG2 and a decrease in endothelial cell proliferation and survival. In vivo, BI 836880 exhibited significant antitumor activity in all patient-derived xenograft models tested, showing significantly greater tumor growth inhibition (TGI) than bevacizumab (VEGF inhibition) and AMG386 (ANG1/2 inhibition) in a range of models. In a Lewis lung carcinoma syngeneic tumor model, the combination of PD-1 inhibition with VEGF inhibition showed superior efficacy versus the blockade of either pathway alone. TGI was further increased with the addition of ANG2 inhibition to VEGF/PD-1 blockade. VEGF/ANG2 inhibition had a strong antiangiogenic effect. Our data suggest that the blockade of VEGF and ANG2 with BI 836880 may offer improved antitumor activity versus the blockade of either pathway alone and that combining VEGF/ANG2 inhibition with PD-1 blockade can further enhance antitumor effects. SIGNIFICANCE STATEMENT: Vascular endothelial growth factor (VEGF) and angiopoietin (ANG)-2 play key roles in angiogenesis and have an immunosuppressive effect in the tumor microenvironment. This study shows that BI 836880, a bispecific nanobody targeting VEGF and ANG2, demonstrates substantial antitumor activity in preclinical models. Combining VEGF/ANG2 inhibition with the blockade of the PD-1 pathway can further improve antitumor activity.
Aln-TMP: A Subcutaneously Administered RNAi Therapeutic Targeting Tmprss6 For The Treatment Of β-Thalassemia (2013)

Abstract The b-Thalassemias are a group of hereditary blood disorders resulting from insufficient beta globin production, ultimately giving rise to the signature clinical sequelae associated with β-Thalassemia which includes anemia, ineffective erythropoiesis, and secondary iron overload. Previously, we demonstrated that intravenous administration of an siRNA targeting hepatic Tmprss6 expression significantly ameliorated the disease phenotype in the Hbbth3/+ mouse model of Thalassemia Intermedia (Blood. 2013; 14;121(7):1200-8). The Tmprss6 gene encodes for the protein Matriptase-2 which negatively regulates Hepcidin gene expression by cleaving the Hepcidin regulatory protein Hemojuvelin; RNAi-mediated suppression of Tmprss6 removes this negative regulator, ultimately leading to an increase in Hepcidin expression. Increased Hepcidin expression leads to a significant decrease in serum iron concentration and Transferrin Saturation (TfSat), which in the β-Thalassemia disease setting, corrects ineffective erythropoiesis, ameliorates anemia, and mitigates secondary iron overload. The role of Tmprss6 in iron metabolism has been extensively characterized in animal and human studies and, together with the observation in the Hbbth3/+ mouse, represents an attractive therapeutic target for the treatment of β-Thalassemia. To this end, we developed ALN-TMP, a subcutaneous RNAi therapeutic targeting hepatic Tmprss6 for the treatment of β-Thalassemia. ALN-TMP employs the GalNAc conjugate siRNA delivery platform that safely and effectively delivers siRNA to the liver for hepatic gene silencing. Preclinical animal data demonstrate ALN-TMP exhibits robust and durable dose-dependent gene suppression as single dose administration of ALN-TMP leads to &gt; 80% Tmprss6 gene suppression for up to 3 weeks post-dose. This leads to concomitant increases in Hepcidin gene expression (&gt;2x baseline levels) and subsequent decreases in total serum iron and TfSat (&gt;50% decrease from baseline). The degree to which ALN-TMP modulates Hepcidin and serum iron mobilization is nearly identical to that observed in the previous Hbbth3/+ mouse studies and suggests ALN-TMP is a potent RNAi therapeutic with the potential of producing disease modifying effects in β-Thalassemia. Disclosures: Butler: Alnylam: Employment. Fishman:Alnylam: Employment. Racie:Alnylam Pharmaceutical, Inc: Employment. Hettinger:Alnylam Pharmaceuticals: Employment. Bettencourt:Alnylam Pharmaceuticals: Employment. Charisse:Alnylam Pharmaceuticals: Employment. Fitzgerald:Alnylam: Employment.
ChemInform Abstract: Ruthenium‐Catalyzed Two‐Component Addition to Form 1,3‐Dienes: Optimization, Scope, Applications, and Mechanism. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The potential use of time reversal techniques in multiple element antenna systems (2005)

Based on outdoor measurements we study the feasibility of applying the time reversal techniques (TR) in multiple element antenna (MEA) wireless communication systems. It is demonstrated that the use of TR in wireless communication has a promising potential in mitigating the effect of channel dispersion and especially in reducing the cochannel interference where a margin of 18 dB interference reduction has been obtained.
CVD Derived Vanadium Oxide Nano-Sphere-Carbon Nanotube (CNT) Nano-Composite Hetero-Structures: High Energy Supercapacitors (2013)

We present herein a facile two-step chemical vapor deposition (CVD) approach to synthesize carbon nanotube (CNT) supported vanadium oxide nanosphere nano-composite hetero-structures as electrochemical supercapacitors. The high electronic conductivity of CNTs has been exploited to provide a 3-D electron transport medium on which vanadium oxide nano-droplets interact with electrolyte to exhibit excellent supercapacitor behavior in aqueous media. Thin nano-scale droplets of vanadium oxide deposited on the CNTs exhibit excellent capacitance values as high as 1400 Fg−1 with good rate capability and excellent charge retention up to 200 cycles. The electrochemical mechanisms and materials properties responsible for the supercapacitor properties of CNT supported vanadium oxide have been discussed at length.
Search for a Heavy Particle Decaying into an Electron and a Muon with the ATLAS Detector ins=7  TeVppcollisions at the LHC (2011)

This Letter presents the first search for a heavy particle decaying into an e ± μ(-/+) final state in sqrt[s] = 7 TeV pp collisions at the LHC. The data were recorded by the ATLAS detector during 2010 and correspond to a total integrated luminosity of 35 pb(-1). No excess above the standard model background expectation is observed. Exclusions at 95% confidence level are placed on two representative models. In an R-parity violating supersymmetric model, tau sneutrinos with a mass below 0.75 TeV are excluded, assuming all R-parity violating couplings are zero except λ(311)' = 0.11 and λ312 = 0.07. In a lepton flavor violating model, a Z'-like vector boson with masses of 0.70-1.00 TeV and corresponding cross sections times branching ratios of 0.175-0.183 pb is excluded. These results extend to higher mass R-parity violating sneutrinos and lepton flavor violating Z's than previous constraints from the Tevatron.
Faculty Opinions recommendation of Synaptotagmin-1 enables frequency coding by suppressing asynchronous release in a temperature dependent manner. (2020)

To support frequency-coded information transfer, mammalian synapses tightly synchronize neurotransmitter release to action potentials (APs). However, release desynchronizes during AP trains, especially at room temperature. Here we show that suppression of asynchronous release by Synaptotagmin-1 (Syt1), but not release triggering, is highly temperature sensitive, and enhances synchronous release during high-frequency stimulation. In Syt1-deficient synapses, asynchronous release increased with temperature, opposite to wildtype synapses. Mutations in Syt1 C2B-domain polybasic stretch (Syt1 K326Q,K327Q,K331Q) did not affect synchronization during sustained activity, while the previously observed reduced synchronous response to a single AP was confirmed. However, an inflexible linker between the C2-domains (Syt1 9Pro) reduced suppression, without affecting synchronous release upon a single AP. Syt1 9Pro expressing synapses showed impaired synchronization during AP trains, which was rescued by buffering global Ca 2+ to prevent asynchronous release. Hence, frequency coding relies on Syt1's temperature sensitive suppression of asynchronous release, an aspect distinct from its known vesicle recruitment and triggering functions.
High-resolution holography and biopsy: Preliminary results (1995)

For holographic biopsy purposes, holograms of biological tissue samples have been recorded in vitro to establish the possibility of differentiating tissues on the holograms. With the use of specific absorbing dyes for staining tissues, the contrast has been improved. On the holograms, tissue architecture has been observed in the cortex of the kidney. Isolated epithelial cells could be seen with a distinct nucleus. Two distinct layers of the gray matter in the human brain have been differentiated. Finally, the case of human ovary carcinoma, the differentiation of putatively normal areas and the cancerous lesion has been evidenced and a submillimetric localization of the lesion could be done. Thus, it has been shown that tissue differentiation on holograms is possible, so that holographic biopsy can be used as a diagnostic aid. The use of an endoscope to perform holographic biopsy would provide the surgeon or physician with a new minimal-invasive quick diagnostic method allowing in situ examination of tissues when conventional biopsy is difficult or even impossible. In the near future, the development of an endoscope for holographic biopsy should lead to clinical investigation in early cancer detection. Prior to measurements on tissues, the recording material (silver-halide) has been evaluated to determine the display and processing parameters in order to obtain the best possible results. The resolution has been estimated below 2.8 μm with a diffraction efficiency of 20%, in the tissue recording configuration.
Search for lepton-flavour-violating decays of the Higgs and Z bosons with the ATLAS detector (2017)

Direct searches for lepton flavour violation in decays of the Higgs and <i>Z</i> bosons with the ATLAS detector at the LHC are presented. The following three decays are considered: [Formula: see text], [Formula: see text], and [Formula: see text]. The searches are based on the data sample of proton-proton collisions collected by the ATLAS detector corresponding to an integrated luminosity of 20.3 [Formula: see text] at a centre-of-mass energy of [Formula: see text] TeV. No significant excess is observed, and upper limits on the lepton-flavour-violating branching ratios are set at the 95[Formula: see text] confidence level: Br[Formula: see text], Br[Formula: see text], and Br[Formula: see text].
ENHANCED HYDROGEN ECONOMICS VIA COPRODUCTION OF FUELS AND CARBON PRODUCTS (2011)

This Department of Energy National Energy Technology Laboratory sponsored research effort to develop environmentally cleaner projects as a spin-off of the FutureGen project, which seeks to reduce or eliminate emissions from plants that utilize coal for power or hydrogen production. New clean coal conversion processes were designed and tested for coproducing clean pitches and cokes used in the metals industry as well as a heavy crude oil. These new processes were based on direct liquefaction and pyrolysis techniques that liberate volatile liquids from coal without the need for high pressure or on-site gaseous hydrogen. As a result of the research, a commercial scale plant for the production of synthetic foundry coke has broken ground near Wise, Virginia under the auspices of Carbonite Inc. This plant will produce foundry coke by pyrolyzing a blend of steam coal feedstocks. A second plant is planned by Quantex Energy Inc (in Texas) which will use solvent extraction to coproduce a coke residue as well as crude oil. A third plant is being actively considered for Kingsport, Tennessee, pending a favorable resolution of regulatory issues.
Ultrahigh-efficiency wavelength conversion in nanophotonic periodically poled lithium niobate waveguides (2018)

Periodically poled lithium niobate (PPLN) waveguides are a powerful platform for efficient wavelength conversion. Conventional PPLN converters, however, typically require long device lengths and high pump powers due to the limited nonlinear interaction strength. Here we use a nanostructured PPLN waveguide to demonstrate an ultrahigh normalized efficiency of 2600%/W−cm^2 for second-harmonic generation of 1.5 μm radiation, more than 20 times higher than that in state-of-the-art diffused waveguides. This is achieved by a combination of sub-wavelength optical confinement and high-fidelity periodic poling at a first-order poling period of 4 μm. Our highly integrated PPLN waveguides are promising for future chip-scale integration of classical and quantum photonic systems.
Polymer-assisted asymmetric reactions. 4. Polymer-bound ephedrine, its use and limitations in supported lithium aluminum hydride reductions (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolymer-assisted asymmetric reactions. 4. Polymer-bound ephedrine, its use and limitations in supported lithium aluminum hydride reductionsJean M. J. Frechet, Edward Bald, and Pierre LecavalierCite this: J. Org. Chem. 1986, 51, 18, 3462–3467Publication Date (Print):September 1, 1986Publication History Published online1 May 2002Published inissue 1 September 1986https://pubs.acs.org/doi/10.1021/jo00368a011https://doi.org/10.1021/jo00368a011research-articleACS PublicationsRequest reuse permissionsArticle Views158Altmetric-Citations27LEARN 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
Smooth Complex Reflectors - An Alternative Approach (1995)

&lt;div class="htmlview paragraph"&gt;Different approaches have been proposed in the past for designing smooth complex reflectors. One major difficulty in designing headlamps with smooth reflectors is maintaining the slope continuity of the reflector surface without compromising the robustness of the beam pattern. In this paper, two simple algorithms are proposed for developing smooth complex reflector headlamps. The first is a numerical marching scheme used to generate smooth complex surfaces based on user specified spread points. In the second approach, a parametrically represented smooth surface is generated with user defined spread points to obtain the desired beam patterns.&lt;/div&gt;
Function through bio-inspired, synthesis-informed design: step-economical syntheses of designed kinase inhibitors (2014)

The human kinome comprises over 500 protein kinases. When mutated or over-expressed, many play critical roles in abnormal cellular functions associated with cancer, cardiovascular disease and neurological disorders. Here we report a step-economical approach to designed kinase inhibitors inspired by the potent, but non-selective, natural product staurosporine, and synthetically enabled by a novel, complexity-increasing, serialized [5 + 2]/[4 + 2] cycloaddition strategy. This function-oriented synthesis approach rapidly affords tunable scaffolds, and produced a low nanomolar inhibitor of protein kinase C.
Reinforced Genetic Algorithm Learning for Optimizing Computation Graphs (2020)

We present a deep reinforcement learning approach to minimizing the execution cost of neural network computation graphs in an optimizing compiler. Unlike earlier learning-based works that require training the optimizer on the same graph to be optimized, we propose a learning approach that trains an optimizer offline and then generalizes to previously unseen graphs without further training. This allows our approach to produce high-quality execution decisions on real-world TensorFlow graphs in seconds instead of hours. We consider two optimization tasks for computation graphs: minimizing running time and peak memory usage. In comparison to an extensive set of baselines, our approach achieves significant improvements over classical and other learning-based methods on these two tasks.
Factors influencing the measured adhesive strength between glass and encapsulant of photovoltaic modules (2013)

Peel tests are used in Photovoltaic (PV) industry to check the encapsulation quality of PV modules. The test results are influenced by variable factors including peel speed, peel angle, mechanical strength of both adhesive and adherend, as well as testing environment. This paper analyses the correlation of measured peel strength with several main factors of peel speed, peel angle and curing state of encapsulant. Laminates with a structure of Glass-Ethylene Vinyl Acetate (EVA) - double Polyethylene Terephthalate (PET/PET) are fabricated at variety conditions to achieve different curing states of EVA. Peel test between glass and EVA of these laminates are examined at the angle of 90o. Peel strength at different speeds and at angles of both 90o and 180o are also evaluated at fixed lamination condition. Finite Element Model (FEM) for 90o peel test is developed using Abaqus software. The interfacial fracture energy between Glass and EVA is calculated using Virtual Crack Closure Technique (VCCT). Results show that peel strength increases with the increasing peel speed and curing state. Fracture energy calculated from FEM modelling also indicates an increasing trend with peel speed.
Joint Design of Communication and Control for Connected Cars in 5G Communication Systems (2016)

This paper is advocating for joint design of communication and control in cyber physical systems, especially self driving automobiles, exploiting adaptive and next generation networking concepts such as mobile edge clouds in 5G commu- nication systems. In this paper, we present our '5G connected- cars' testbed that was demonstrated in multiple international events including the Mobile World Congress, Barcelona in 2016. It constitutes a complete network architecture and cloud software services that facilitates custom built miniature cars to run autonomously on a track with an intersection without collisions by using hybrid car-to-car and car-to-infrastructure communi- cation. We tackle the latency problem in classical connected cyber physical systems by the use of mobile edge cloud in the full blown emulated 5G air interface in the cmWave band in Nokia Airframe. Finally, presenting some measurements from the testbed, we advocate for a dedicated 5G air interface for reliable and scalable steering and control, as opposed to the use of ISM bands such as IEEE802.11P.
Origin of the ‘inactivation’ of ribonuclease A at low salt concentration (2000)

The effect of salt concentration on catalysis by ribonuclease A (RNase A) has been reexamined. At low salt concentration, the enzyme is inhibited by low-level contaminants in common buffers. When an uncontaminated buffer system is used or H12A RNase A, an inactive variant, is added to absorb inhibitory contaminants, enzymatic activity is manifested fully at low salt concentration. Catalysis by RNase A does not have an optimal salt concentration. Instead, k(cat)/K(M)10(9) M(-1)s(-1) for RNA cleavage at low salt concentration. These findings highlight the care that must accompany the determination of meaningful salt-rate profiles for enzymatic catalysis.
Unwrapping phases by relaxed mean field inference (2002)

Some types of medical and topographic imaging devices produce images in which the pixel values are "phase-wrapped", i.e., the measured modulus is a known scalar. Phase unwrapping can be viewed as the problem of inferring the number of shifts between each and every pair of neighboring pixels, subject to an a priori preference for smooth surfaces, and subject to a zero curl constraint, which requires that the shifts must sum to 0 around every loop. We formulate phase unwrapping as a mean field inference problem in a probability model, where the prior favors the zero curl constraint. We compare our mean field technique with the least squares method on a synthetic 100/spl times/100 image, and give results on a larger 512/spl times/512 image.
Molecular mechanism for the capture and excision of the transforming gene of avian sarcoma virus as suggested by analysis of recombinant clones (1980)

Structural analysis of two cDNA clones, derived from reverse transcripts of avian sarcoma virus 21S mRNA's, reveals unusual features in the organization and expression of the integrated avian sarcoma virus (ASV) proviral DNA and predicts a mechanism for recombination events that will lead to either the capture or the excision of the transforming gene of this virus. The latter is supported by our observation that there is an extensive homologous region on either side of the transforming gene that will allow site-specific deletion or integration to occur. Comparison of the clone derived from the src-specific 21S mRNA coding for the transforming gene product to that derived from the env-specific 21S mRNA coding for the envelope glycoprotein show that the common c region present at the 3' terminus of the ASV genome is 326 bases long. Within this c region are nucleotide sequences that may play key roles in the life cycle of this virus. These regulatory sequences include (i) probable promoter sites for the initiation of transcription, (ii) a polyadenylation signal, and (iii) a sequence that is complementary to the 3' termini of both the env and the src regions, which will allow the generation of transformation-defective deletions.