gebhart/patrepeval huggingface dataset:
Decision letter: An open label trial of anakinra to prevent respiratory failure in COVID-19 (2021)

People infected with the SARS-CoV-2 virus, which causes COVID-19, can develop severe respiratory failure and require a ventilator to keep breathing, but this does not happen to every infected individual. Measuring a blood protein called suPAR (soluble urokinase plasminogen activator receptor) may help identify patients at the greatest risk of developing severe respiratory failure and requiring a ventilator. Previous investigations have suggested that measuring suPAR can identify pneumonia patients at highest risk for developing respiratory failure. The protein can be measured by taking a blood sample, and its levels provide a snapshot of how the body’s immune system is reacting to infection, and of how it may respond to treatment. Anakinra is a drug that forms part of a class of medications called interleukin antagonists. It is commonly prescribed alone or in combination with other medications to reduce pain and swelling associated with rheumatoid arthritis. Kyriazopoulou et al. investigated whether treating COVID-19 patients who had developed pneumonia with anakinra could prevent the use of a ventilator and lower the risk of death. The findings show that treating COVID-19 patients with an injection of 100 milligrams of anakinra for ten days may be an effective approach because the drug combats inflammation. Kyriazopoulou et al. examined various markers of the immune response and discovered that anakinra was able to improve immune function, protecting a significant number of patients from going on a ventilator. The drug was also found to be safe and cause no significant adverse side effects. Administering anakinra decreased of the risk of progression into severe respiratory failure by 70%, and reduced death rates significantly. These results suggest that it may be beneficial to use suPAR as an early biomarker for identifying those individuals at highest risk for severe respiratory failure, and then treat them with anakinra. While the findings are promising, they must be validated in larger studies.
From 2D to Monolithic 3D (2015)

Design of conventional 2D integrated circuits is becoming more and more challenging as we strive to keep on following Moore's law. Cost, thermal behavior, multiple patterning, increasing number of design rules, transistor characteristics, variability and back end properties coupled with a constant need for a higher integration of functions / peripherals are creating an increasingly complex equation to solve for designers. Moving to the next node and taking advantage of the technology are now far from being straightforward as time to market has never been so short for industry. In order to overcome or at least postpone the time when we'll have to face the "next node migration constraints", a possible solution could be staying at the same node and go 3D with possible benefits such as wire length reduction, power savings and increased operating frequency. Since more than ten years now, interconnect technologies like Through Silicon Via (TSV), High Density (HD)-TSV and Copper to Copper (Cu-Cu) have arisen to take advantage of this possible 3-dimensional physical implementation with proofs of concept [1] or more recently industrial products [2]. Main drawback of these technologies is that they are not shrinking at the same speed as transistors are, making them somehow power hungry; moreover the more they will shrink, the more precision will be needed for chip to chip alignment. To reach the highest possible standard cell and tier to tier interconnect densities required for cost-effective chips, 3D sequential integration process [3][4][5] (also known as Monolithic 3D or CoolCubeTM) is currently developed with main features being sequential fabrication of MOS layers and correlation of tier to tier interconnect size with process node allowing fine-grain 3D partitioning of designs. These particularities make it a durable opportunity to slow down next node design migration while still improving integration. To fully benefit from CoolCubeTM technology, a whole new way of designing circuits, from synthesis to place and route, will be required as some new challenges will arise. The point of this presentation is to show the possible use and limitations of the aforementioned technologies with a focus on Monolithic 3D and to give some insights about market expectations, challenges and available design techniques.
Synthesis of 2-anilinopyridine–arylpropenone conjugates as tubulin inhibitors and apoptotic inducers (2015)

2-Anilinopyridine–arylpropenone conjugates as novel tubulin inhibitors and apoptotic inducers.
Modeling Real Objects Using Video See-Through Augmented Reality (2002)

This paper presents an interactive “what-you-see-is-what-you-get” (WYSIWYG) method for creating textured 3-D models of real objects using video see-through augmented reality. We use a tracked probe to sample the objects' geometries, and we acquire video images from the head-mounted cameras to capture textures. Our system provides visual feedback during modeling by overlaying the model onto the real object in the user's field of view. This visual feedback makes the modeling process interactive and intuitive.
Manipulation of Ag nanoparticles utilizing noncontact atomic force microscopy (1998)

We have developed a scheme to manipulate metallic aerosol particles on silicon dioxide substrates using an atomic force microscope. The method utilizes the noncontact mode both for locating and moving nanoparticles of size 10–100 nm. The main advantage of our technique is the possibility of “seeing” the moving particle in real time. Our method avoids well sticking problems that typically hamper the manipulation in the contact mode.
Novel TPO receptor agonist TA-316 contributes to platelet biogenesis from human iPS cells (2017)

Signaling by thrombopoietin (TPO) in complex with its receptor, c-MPL, is critical for hematopoietic stem cell (HSC) homeostasis and platelet generation. Here we show that TA-316, a novel chemically synthesized c-MPL agonist (CMA), is useful for ex vivo platelet generation from human-induced pluripotent stem (iPS) cell-derived immortalized megakaryocyte progenitor cell lines (imMKCLs). Moreover, the generation is clinically applicable, because self-renewal expansion and platelet release is tightly controllable. TA-316 but not eltrombopag, another CMA, promoted both the self-renewal and maturation of imMKCLs, leading to more than a twofold higher platelet production than that achieved with recombinant human TPO (rhTPO). Interestingly, TA-316 seemed to favor MK-biased differentiation from bone marrow CD34<sup>+</sup> HSC/progenitors and imMKCLs through the upregulation of vascular endothelial growth factor A and fibroblast growth factor 2. This result suggests TA-316 could facilitate the development of an efficient and useful system to expand platelets from imMKCLs.
Discodermolide/Dictyostatin Hybrids:  Synthesis and Biological Evaluation (2003)

Two hybrid analogues of discodermolide and dictyostatin (&lt;b&gt;3&lt;/b&gt;, &lt;b&gt;26&lt;/b&gt;) have been designed and synthesized. These are the first macrocyclic analogues\nof discodermolide and biological activities were evaluated and compared with linear discodermolide analogues.
Enzymatic Detoxification of HC-toxin, the Host-Selective Cyclic Peptide from Cochliobolus carbonum (1991)

Resistance to the fungal plant pathogen Cochliobolus carbonum race 1 and to its host-selective toxin, HC-toxin, is determined by Hm, a single dominant gene in the host plant maize, (Zea mays L). Radiolabeled HC-toxin of specific activity 70 milliCuries per millimole, prepared by feeding tritiated d,l-alanine to the fungus, was used to study its fate in maize leaf tissues. HC-toxin was converted by resistant leaf segments to a single compound, identified by mass spectrometry and nuclear magnetic resonance as the 8-hydroxy derivative of HC-toxin formed by reduction of the 8-keto group of 2-amino-9, 10-epoxy-8-oxo-decanoic acid, one of the amino acids in HC-toxin. Reduction of HC-toxin occurred in cell-free preparations from etiolated (Hm/hm) maize shoots, and the activity was sensitive to heat and proteolytic digestion, dependent on NADPH, and inhibited by p-hydroxymercuribenzoate and disulfiram. The enzyme (from the Hm/hm genotype) was partially purified by ammonium sulfate precipitation and diethylaminoethyl-ion exchange chromatography. By gel filtration chromatography, the enzyme had a molecular weight of 42,000. NADH was approximately 30% as effective as NADPH as a hydride donor, and flavin-containing cofactors had no effect on activity. When HC-toxin was introduced to maize leaf segments through the transpiration stream, leaf segments from both resistant and susceptible maize inactivated toxin equally well over a time-course of 9 hours. Although these data suggest no relationship between toxin metabolism and host selectivity, we discuss findings in apparent conflict with the current data and describe why the relationship between enzymatic reduction of HC-toxin and Hm remains unresolved.
Reproduction of real-world haptic information in access space (2010)

This paper proposes environment-copying system using novel environmental data memory, which stores and reproduces haptic information in the real-world. The proposed environmental data memory treats the environmental characteristics based on momentum information, so that the size of the environmental data memory is able to be reduced. The proposed system reproduces the force information from the environment, and stimulates the human operator according to the environmental data memory in access space. Therefore, the human operator is able to feel the haptic sensation. By the experiments, the validity of the proposed method is confirmed.
An Aggregate Computing Approach to Self-Stabilizing Leader Election (2018)

Leader election is one of the core coordination problems of distributed systems, and has been addressed in many different ways suitable for different classes of systems. It is unclear, however, whether existing methods will be effective for resilient device coordination in open, complex, networked distributed systems like smart cities, tactical networks, personal networks and the Internet of Things (IoT). Aggregate computing provides a layered approach to developing such systems, in which resilience is provided by a layer comprising a set of adaptive algorithms whose compositions have been shown to cover a large class of coordination activities. In this paper, we show how a feedback interconnection of these basis set algorithms can perform distributed leader election resilient to device topology and position changes. We also characterize a key design parameter that defines some important performance attributes: Too large a value impairs resilience to loss of existing leaders, while too small a value leads to multiple leaders. We characterize the smallest value of this parameter for which the only stationary points have single leaders, and demonstrate resilience of this algorithm through simulations.
Beyond the mirrored Faraday rotator: birefringence compensation in optical retracing circuits (2018)

General compensation rules in retracing circuits containing different kinds of birefringence, either reciprocal or non-reciprocal, are illustrated. The whole picture involves the use of a mirror, a mirrored Faraday rotator and a mirrored quarter-wave plate.
P4‐197: Preclinical characterization of LY2886721: A BACE1 inhibitor in clinical development for early Alzheimer's disease (2012)

BACE1 is a key protease targeting the amyloid processing pathways in AD. Previously we published on LY2811376, the first small molecule BACE1 inhibitor reported to provide robust CSF Abeta changes in healthy subjects. LY2811376 progressed to clinical trials but was terminated due to non-clinical tox findings. Here we report the preclinical pharmacology of LY2886721, a new BACE1 inhibitor that is in clinical development for early AD. Enzyme assays were conducted with recombinant enzymes using a FRET platform. Cell based assays were conducted with either a HEK293Swe cell line or primary neuronal cultures prepared from PDAPP mice. D ose response and time course studies were conducted in young PDAPP transgenic mice with brain collected at various times after oral gavage and extracts analyzed by ELISA for relevant PD biomarkers including Abeta, C99 and sAPPbeta. Plasma and CSF PK/PD studies were conducted in beagle dogs using a multi-week paradigm which involved establishing vehicle-treated baseline CSF Abeta values for within dog comparison to subsequent CSF samples taken from LY-treated dogs. LY2886721 inhibited recombinant hBACE1 with an IC50 of 20.3 nM. In cellular assays, LY2886721 inhibited Abeta with an IC50 of 18.7 nM and 10.7 nM, HEK293Swe and PDAPP neuronal culture, respectively. Oral administration of LY2886721 to PDAPP mice produced dose-dependent reductions in brain Abeta, C99 and sAPPbeta. Brain Abeta levels were decreased ∼20% -65% relative to vehicle-treated groups three hours after a 3-30 mg/kg dose of LY2886721. Brain C99 and sAPPb levels also were reduced in a dose-dependent manner consistent with BACE1 inhibition in vivo. The pharmacodynamic responses to LY2886721 persisted out to 9 hours post dose in brains of PDAPP mice. Pharmacodynamic studies in beagle dog revealed robust and sustained reductions in plasma Abeta following 1 mg/kg LY2886721 dosing. Central effects of BACE1 inhibition in dog were manifested by a 50% reduction in CSF Abeta at 9 hours after a 0.5 mg/kg dose of LY2886721. LY2886721 is a potent inhibitor of BACE1 which demonstrates robust in vitro and in vivo BACE1 inhibition in pre-clinical models. Phase 2 clinical trials in AD patients are planned for 2012.
Antisense oligodeoxynucleotide against HST‐1/FGF‐4 suppresses tumorigenicity of an orthotopic model for human germ cell tumor in nude mice (2003)

Collectively, these results indicate that the antisense method against HST-1/FGF-4 gene expression will be a novel therapeutic approach for male germ cell tumors. The use of Atelocollagen-mediated administration of the antisense HST-1/FGF-4 ODNs may be useful in enhancing the effects of antisense therapy.
Study on Maximizing Exergy in Automotive Engines (2007)

&lt;div class="htmlview paragraph"&gt;The use of waste heat for automobile engine that applied Rankine cycle from the viewpoint of exergy (available energy) was researched. In order to recover heat to high quality energy, a heat-management engine whose exhaust port was replaced with an innovative evaporation device was developed. With this engine, high temperature and high pressure steam (400 degree C, 8MPa) could be generated from a large amount of the exhaust loss. In addition, high temperature water (189 degree C) was obtained from cooling loss. Consequently, the system that recovered more exergy from waste heat was established.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;To verify the system, the Rankine cycle system was installed in a hybrid vehicle and the automatic control system to change steam temperature and pressure according to the load variation was constructed. As the result of vehicle testing, thermal efficiency was increased from 28.9% to 32.7% (by 13.2% increase) at 100km/h constant vehicle speed. In this paper, it is concluded that Rankine cycle using waste heat was very effective to maximize exergy in automotive engine.&lt;/div&gt;
Domain walls and anchoring transitions mimicking nematic biaxiality in the oxadiazole bent-core liquid crystal C7 (2015)

We investigate the origin of "secondary disclinations" that were recently described as new evidence of a biaxial nematic phase in an oxadiazole bent-core thermotropic liquid crystal C7. Using an assortment of optical techniques such as polarizing optical microscopy, LC PolScope, and fluorescence confocal polarizing microscopy, we demonstrate that the secondary disclinations represent non-singular domain walls formed in a uniaxial nematic phase during the surface anchoring transition, in which surface orientation of the director changes from tangential (parallel to the bounding plates) to tilted. Each domain wall separates two regions with the director tilted in opposite azimuthal directions. At the centre of the wall, the director remains parallel to the bounding plates. The domain walls can be easily removed by applying a moderate electric field. The anchoring transition is explained by the balance of (a) the intrinsic perpendicular surface anchoring produced by the polyimide aligning layer and (b) tangential alignment caused by ionic impurities forming electric double layers. The model is supported by the fact that the temperature of the tangentially tilted anchoring transition decreases as the cell thickness increases and as the concentration of ionic species (added salt) increases. We also demonstrate that the surface alignment is strongly affected by thermal degradation of the samples. This study shows that C7 exhibits only a uniaxial nematic phase and demonstrates yet another mechanism (formation of "secondary disclinations") by which a uniaxial nematic phase can mimic a biaxial nematic behaviour.
Tenascins and the Importance of Adhesion Modulation (2011)

Tenascins are a family of extracellular matrix proteins that evolved in early chordates. There are four family members: tenascin-X, tenascin-R, tenascin-W, and tenascin-C. Tenascin-X associates with type I collagen, and its absence can cause Ehlers-Danlos Syndrome. In contrast, tenascin-R is concentrated in perineuronal nets. The expression of tenascin-C and tenascin-W is developmentally regulated, and both are expressed during disease (e.g., both are associated with cancer stroma and tumor blood vessels). In addition, tenascin-C is highly induced by infections and inflammation. Accordingly, the tenascin-C knockout mouse has a reduced inflammatory response. All tenascins have the potential to modify cell adhesion either directly or through interaction with fibronectin, and cell-tenascin interactions typically lead to increased cell motility. In the case of tenascin-C, there is a correlation between elevated expression and increased metastasis in several types of tumors.
ChemInform Abstract: SYNTHESIS OF 5‐ARYL‐12H‐QUINAZOLINO(3,2‐A)QUINAZOLIN‐12‐ONES AS ANTIINFLAMMATORY AGENTS (1983)

Abstract Die Reaktion der Anthranilsäuren (I) mit Z‐Chlorchinazolin (II) liefert die im Titel genannten Verbindungen (III), die entzündungshemmende, aber keine antimikrobielle Wirksamkeit besitzen.
Isolation of a gene encoding a developmentally regulated T cell-specific protein with a guanine nucleotide triphosphate-binding motif. (1995)

In this study, we describe a novel full length cDNA clone designated Tgtp that encodes a predicted 415-amino acid a T cell-specific guanine nucleotide triphosphate-binding protein (TGTP) bearing the characteristic motifs of a guanine nucleotide triphosphate (GTP) binding protein. Tgtp is expressed preferentially, if not exclusively, in T cells, and is up-regulated in both unfractionated and in purified CD4+8+ thymocytes upon TCR cross-linking. In contrast, expression of Tgtp is peripheral T cells is maintained at relatively high levels and is not grossly affected by TCR cross-linking. Antiserum generated against synthetic peptides from the predicted TGTP amino acid sequence recognized a single protein with a molecular mass of approximately 50 kDa, corresponding well with the computed molecular mass of 47 kDa. The only known relative of Tgtp is MUSGTP, which is reportedly expressed in B cells and bears a GTP binding motif. Thus, the discovery of Tgtp resolves a subfamily of molecules with GTP binding motifs and apparent lymphoid lineage-restricted expression. Given the restricted expression pattern in T cells, the up-regulated expression observed in response to TCR signaling in immature thymocytes, and the presence of the motifs characteristic of GTP binding proteins, we suggest that TGTP may have an important function in T cell development and/or T cell activation.
Flexible Piezoelectric Acoustic Sensors and Machine Learning for Speech Processing (2019)

Flexible piezoelectric acoustic sensors have been developed to generate multiple sound signals with high sensitivity, shifting the paradigm of future voice technologies. Speech recognition based on advanced acoustic sensors and optimized machine learning software will play an innovative interface for artificial intelligence (AI) services. Collaboration and novel approaches between both smart sensors and speech algorithms should be attempted to realize a hyperconnected society, which can offer personalized services such as biometric authentication, AI secretaries, and home appliances. Here, representative developments in speech recognition are reviewed in terms of flexible piezoelectric materials, self-powered sensors, machine learning algorithms, and speaker recognition.
EP007/#994 Bay 1895344, a novel ATR inhibitor, demonstrates in vivo activity against ATRX altered uterine leiomyosarcoma (2022)

<h3>Objectives</h3> Uterine leiomyosarcoma (uLMS) is a rare, aggressive gynecologic malignancy. Up to 51% of uLMS harbor somatic mutations in ATRX, a tumor suppressor in the transcription regulation pathway, which increase sensitivity to ATR inhibitors. We sought to investigate the in vivo activity of a novel ATR inhibitor, BAY 1895344, against ATRX altered uLMS. <h3>Methods</h3> ATRX altered PDX models LEY11 and LEY 16 were grafted into female CB-17/SCID mice and triaged to treatment with control or BAY1895344 (10 or 20 mg/kg daily). Treatments were given via oral gavage twice daily for three days weekly and tumor measurements and weights obtained twice weekly. ATR and DAXX expression were determined by Western blotting and RTPCR. Tumor volume differences were calculated with a two-way ANOVA, and p-value &lt;0.05 was considered statistically significant. OS was compared via a Kaplan-Meier survival curve. <h3>Results</h3> Tumor growth inhibition was significantly greater in the BAY1895344 groups in both LEY 11 (n=12) and LEY 16 (n=13) (p=0.0003 and p = 0.006, respectively). Median overall survival was significantly longer in both LEY 11 (12.5 vs. 42 days, p = 0.001) and LEY 16 (32 vs. 60 days, p &lt; 0.001). There was no significant toxicity. ATRX was overexpressed in LEY 11 (Avg dCt 10.09 vs. 6.56) as well as DAXX (Avg dCt 8.97 vs. 6.46). <h3>Conclusions</h3> BAY1895344 demonstrates promising in vivo activity against a PDX model of uLMS that harbors ATRX mutations, with no significant toxicity. Phase I trials of BAY1895344 are currently ongoing, and its clinical use in uLMS warrants further investigation.
ChemInform Abstract: A SIMPLE METHOD FOR THE EFFICIENT SYNTHESIS OF UNSATURATED β‐DICARBONYL COMPOUNDS (1981)

Abstract (XII) aus den entsprechenden gesättigten Ausgangsverbindungen herangezogen.
Model family of high-temperature superconductors:TlmCan−1Ba2CunO2(n+1)+m(m=1,2;n=1,2,3) (1988)

We describe the structures and superconducting properties of six compounds in the Tl-Ca-Ba-Cu-O system of the general form, ${\mathrm{Tl}}_{m}{\mathrm{Ca}}_{n\ensuremath{-}1}{\mathrm{Ba}}_{2}{\mathrm{Cu}}_{n}{\mathrm{O}}_{2(n+1)+m}$, where $m=1 or 2$ and $n=1,2, or 3$. One of the compounds displays the highest known superconducting transition temperature, ${T}_{c}\ensuremath{\simeq}125$ K. The structures of these compounds consist of copper perovskitelike blocks containing 1, 2, or 3 Cu${\mathrm{O}}_{2}$ planes separated by one or two Tl-O layers and thus form a model family of structures in which both the size and separation of the copper oxide blocks can be independently varied. The superconducting transition temperature increases with the number of Cu${\mathrm{O}}_{2}$ planes in the perovskitelike block for both the Tl-O monolayer and bilayer compounds. For each pair of compounds ($m=1,2$) with the same number of Cu${\mathrm{O}}_{2}$ planes (same $n$), the transition temperatures are similar but are consistently 15-20 K lower in the materials with single Tl-O layers. Variations in the transition temperatures in the double and triple Cu${\mathrm{O}}_{2}$-layer compounds are observed to correlate with increased densities of intergrowths of related structures.