gebhart/patrepeval huggingface dataset:
Abstract LB-201: BIL06v immunizations generate antibodies specific for non-functional P2X7(nfP2X7) that target solid tumorsin vivo (2019)

P2X7 is an ATP-gated purinergic receptor characterized by a biphasic response. Short term exposure to high ATP concentrations triggers opening of a cation channel, whilst prolonged exposure triggers opening of a non-selective pore that disrupts intracellular homeostasis, leading to cell death. Increasing numbers of studies have described a role for P2X7 in malignant tumors, including breast, prostate, colorectal and lung, and P2X7 has been shown to play critical roles in mediating various cancer cellular responses, such as cell proliferation, migration, invasion, and survival. We have described a form of P2X7 that is highly expressed on several cancers, which we term non-functional P2X7 (nfP2X7) that is unable to open a non-selective pore. Non-functional-P2X7 can form when P2X7-expressing cells undergo prolonged exposure to high ATP concentrations found in the local tumor microenvironment. This conformational change results in the exposure of a unique epitope composed of amino acids 200-216, known as the E200 peptide epitope. The E200 peptide epitope has been shown to be a safe and selective target for antibodies against solid tumors. Using the E200 peptide epitope we have prepared a peptide vaccine adjuvanted by Alhydrogel 2%, which we have termed BIL06v, for the therapeutic treatment of solid tumors. A similar vaccination approach was used to generate antibodies for a topical therapeutic that was shown to be safe with indications of efficacy in a Phase 1 clinical trial to treat basal cell carcinoma. Using preclinical in vivo models, we have investigated the tractability of BIL06v as a therapeutic against tumors. In mice and human, BIL06v can break immune tolerance and drive the production of antibodies specific for nfP2X7. A formal toxicology study has demonstrated both immunogenicity and safety in rats following repeated treatment with BIL06v. Furthermore, BIL06v treatment has been shown to improve host outcomes in syngeneic mouse models of disease. Therefore, targeting nfP2X7 with a peptide conjugate vaccine, such as BIL06v, presents a novel and safe therapeutic approach for the treatment of multiple malignancies.Citation Format: Chris J. Oliphant, Elle Freeman, Simon Gilbert, Romain Lara, Edwin Huang, Julian Barden, Shaun McNulty. BIL06v immunizations generate antibodies specific for non-functional P2X7 (nfP2X7) that target solid tumors in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-201.
The Cyclic Mass (2019)

England in the fifteenth century was the cradle of much that would have a profound impact on European music for the next several hundred years. Perhaps the greatest such development was the cyclic cantus firmus Mass, and scholarly attention has therefore often been drawn to identifying potentially English examples within the many anonymous Mass cycles that survive in continental sources. Nonetheless, to understand English music in this period is to understand it within a changing nexus of two-way cultural exchange with the continent, and the genre of the Mass cycle is very much at the forefront of this. Indeed, the question of ‘what is English’ cannot truly be answered without also answering the question of ‘what is continental’. This book seeks, initially, to answer both of these questions. Perhaps more importantly, it argues that a number of the works that have induced the most scholarly debate are best seen through the lens of intensive and long-term cultural exchange and that the great binary divide of provenance can, in many cases, productively be broken down. A great many of these works, though often written on the continent, can, it seems, only be understood in relation to English practice – a practice which has had, and will continue to have, major importance in the ongoing history of European Art Music.
c-kit D816V Provides a Strong Signal for Myelomastocytic Differentiation and Cluster Formation in Murine Ba/F3 Cells. (2004)

Abstract The pathologic hallmark of systemic mastocytosis (SM) is differentiation and cluster formation of mast cells (MC) in hematopoietic tissues. The somatic c-kit mutation D816V is detectable in a majority of all SM patients independent of the proliferation-status of MC or subtype (indolent or aggressive) of disease. To investigate the role of c-kit D816V in the pathogenesis of SM, we established a Ba/F3 cell line with doxycycline-inducible expression of c-kit D816V. We found that c-kit D816V provides a strong signal for mast cell differentiation and cluster formation in Ba/F3 hematopoietic progenitor cells without enhancing their growth thereby resembling the clinical presentation of indolent SM (ISM). As assessed by gene chip analysis, induction of c-kit D816V resulted in expression of various differentiation antigens including mouse mast cell protease 5, mi transcription factor, histidine decarboxylase (HDC), secretory granule proteoglycan, IL-4 receptor, ICAM-1, and CD63 consistent with an early phase of mastopoiesis. By contrast, c-kit D816V did neither induce expression of granulo-monocytic antigens such as myeloperoxidase, IL-3 receptor, or GM-CSF receptor, nor expression of ‘late stage’ mast cell antigens such as FcεRI. The c-kit D816V-induced synthesis of histamine in Ba/F3 cells was confirmed by RIA. To examine the role of c-kit D816V in the pathogenesis of mastocytosis, we extended our analysis to bone marrow biopsy sections obtained from patients with ISM. In these experiments, the D816V-mutated form of c-kit was detected more frequently in micro-dissected tryptase-positive MC obtained from dense compact infiltrates (44.2%) than in diffusely spread MC in these patients (22.6%) (p&amp;lt;0.05). In summary, our data establish a role for c-kit D816V in differentiation and cluster formation of neoplastic (mast) cells. Additional genetic hits, apart from c-kit D816V, may be responsible for aggressive growth of MC in advanced MC neoplasms.
1P1-I05 The Estimation of Surface Shape Using Lined Strain Sensors (2008)

We propose a method to measure the shapes of solid surface with a strain sensor. Our device is comprised of two different kinds of cantilevers, which are 8 pressure and 7 shear stress sensors, arrayed alternately in line by 5.0 mm and covered by silicone rubber. Our device offers the detection of concavo-convex shapes by scanning the surface of the object once. With pressing, releasing and sliding motion, our device detected one convex shape within a 1.0 mm error and two convex shapes within a 3.0 mm error. In addition, we demonstrated that various types of object shapes were detected by our device with tracing motion.
Towards Sub-Minute PET Examination Times (2011)

The main performance parameters in positron camera system design are sensitivity and spatial resolution. This paper concerns sensitivity, which is a function of the scintillation material, the solid angle subtended by the detector array, and the scintillator packing fraction. The solid angle can be increased by extending the axial extent of cylindrical detector systems. Most commercial positron camera systems are based on rings of detector blocks with lutetium oxyorthosilicate, LSO:Ce or LYSO:Ce, as the scintillator of choice. By adding more rings, the solid angle and thus the absolute sensitivity increases while the singles detection efficiency remains fairly constant assuming the same crystal thickness. It has been shown that Ca co-doping of LSO:Ce reduces the scintillation decay time to ~30 ns with a light output over 30000 ph/MeV. This improvement may give a time-of-flight (TOF) advantage with time resolution of 500 ps or less. If the count rate sensitivity of a large axial field-of-view (AFOV) system is combined with the TOF sensitivity increase, we have the means to create examination times in the sub-minute range with no compromise in image quality. In the present study we have compared the existing Siemens molecular CT (mCT) systems to future 6, 8, 12, 20 and higher block ring systems with and without TOF. The mCT 4 block ring system has been used as a reference. The time for acceptable image quality with this system is then extrapolated to other systems based on planar sensitivity. However, the planar sensitivity is related to the solid angle, and reaches saturation for large AFOVs. This implies that there is an upper count rate sensitivity limit. A 20 block ring system may cover a 70 cm examination range at a certain planar count rate and could provide acceptable quality images in approximately 10 seconds by combining the high planar sensitivity count rate provided by the multi-ring feature, the high stopping power of LSO and the TOF gain due to the improved timing resolution. The increased sensitivity may be used to reduce patient dose.
All‐Carbon Quaternary Stereogenic Centers by Enantioselective Cu‐Catalyzed Conjugate Additions Promoted by a Chiral N‐Heterocyclic Carbene. (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.
Abstract 910: Selective inhibition of Rac1 and Cdc42 in ovarian cancer using the R-enantiomer of ketorolac (2012)

Abstract Ovarian cancer is the 5th leading cause of cancer death for women in the United States and is frequently diagnosed at late stage with multiple secondary metastases. Ras-homologous (Rho) family GTPases contribute to metastatic dissemination through regulation of actin reorganization, cell motility, cell-cell and cell-extracellular matrix adhesion. Rho GTPases are altered in a number of human cancers and our work provides the first evidence for dysregulation of Rac1 and Cdc42 in ovarian cancer. These findings suggest that Rac1 and Cdc42 inhibitors represent potential therapeutics for ovarian cancer. Using high throughput screening we identified the R-enantiomers of ketorolac and naproxen as novel inhibitors of Rac1 and Cdc42. Although it has been noted that R-enantiomers of nonsteroidal anti-inflammatory drugs are poor inhibitors of cyclooxygenase (COX) activity, little is known about the pharmacologic activities or targets of the R-enantiomers. The objective of this study was to investigate the effects of R-ketorolac on ovarian cancer. The effects of racemic, R- and S-ketorolac were investigated using SKOV3ip ovarian cancer cells. The compounds NSC23766 and MLS0000693334 were used as positive controls for Rac1 and Cdc42 respectively. An in vitro G-LISA assay indicated R-ketorolac, and not S-ketorolac, inhibits Rac1 and Cdc42 activity. In cells, R-Ketorolac, not S-ketorolac, inhibits cell:cell adhesion and cell migration. An intra-peritoneal xenograft model of tumor implantation was used to determine the effects of drugs in vivo. Racemic ketorolac decreased the number of implanted tumors by 70%. To elucidate the mechanism of GTPase inhibition by R-ketorolac, a targeted microarray analysis was performed. Preliminary results show an alteration to the gene expression profile of human cytoskeletal regulators in response to ketorolac treatment. These effects may be due to inhibition of Rac1 and Cdc42 directly or through upstream or downstream inhibition. This analysis also provides biomarkers that can be used to analyze tumor tissues from primary patients and animal studies. Together, these findings indicate that R-ketorolac is a novel inhibitor of Rac1 and/or Cdc42, and inhibit cellular processes necessary for ovarian cancer metastasis. The mechanism behind ketorolac inhibition will require further investigation. In the future, this drug may offer benefit to ovarian cancer patients through inhibition of these GTPase targets Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 910. doi:1538-7445.AM2012-910
Low‐Dose Interleukin‐2 for Refractory Autoimmune Hepatitis (2018)

Lim, Tiong Y.; Martinez‐Llordella, Marc; Kodela, Elisavet; Gray, Elisabeth; Heneghan, Michael A.; Sanchez‐Fueyo, Alberto , M.D., Ph.D. Author Information
Advanced overlay metrology for 3D NAND bonding applications (2023)

3D heterogeneous integration is an evolving segment in integrated circuit development and advanced packaging to drive More than Moore (MtM) chip scaling. Heterogeneous integration allows IC manufacturers to stack and integrate more silicon devices in a single package, increasing the transistor density and product performance. Product designers seek to gain higher bandwidth, increased power, improved signal integrity, more flexible designs (mix/match different chip functions, sizes, and technology nodes), and lower overall costs. The 3D heterogeneous integration roadmap strives to reduce the bonding bumps/pads pitch to a sub-micrometer level, enabling a higher bump I/O density. Key process development activity is occurring in the wafer-to-wafer (W2W) bonding process to reduce interconnect pitch to 10μm and below. In the W2W process, a wafer bonder is used to align and bond two whole wafers. The bonded wafers are then cut up into stacked chips using a dicing process and undergo testing and further packaging. To successfully unite these two bond surfaces with a very small pitch, tight control of the bond pad alignment is required to make sure the copper pads to be bonded line up perfectly, driving an increased need for overlay metrology precision and die-bonder control. Overlay metrology challenges include thick silicon and tight overlay (OVL) error specifications to enable tight and fast on-product overlay (OPO) control for 3D NAND product development. This work will evaluate the various aspects impacting OPO, including the pre and post-bonding error budget, accuracy, measurability, robustness, and throughput.
Multi‐Source Time Synchronization in IEEE Std 802.15.4‐2015 TSCH Networks (2020)

IEEE std 802.15.4‐2015 Time Slotted Channel Hopping (TSCH) extends and replaces multiple proprietary industrial standards to support ultra‐reliable and ultra‐low power operation in Industrial Internet of Things. Under TSCH, all devices must remain continuously synchronized with their time source neighbor. To do so, the nodes either periodically exchange control packets or data packets to compensate for clock drift. However, single time source neighbor scheme endangers de‐synchronization in the wireless network. In this letter, we propose using multiple time source parents to improve the synchronization of the network.
CDC Teal hard red spring wheat (1993)

Teal is an early-maturing hard red spring wheat best adapted to the Black soil zone of western Canada. It combines early maturity with good yield potential, increased kernel size and leaf and stem rust resistance. It was developed at the University of Saskatchewan from a three-way cross involving BW514 (Nainari 60/Huelquen), Benito and BW38 (UM953A/Neepawa; UM953A = Sonora 64/Tezanos Pintos Precos). Key words: Triticum aestivum, cultivar description, bread wheat
Relative analgesic potency of intramuscular heroin and morphine in cancer patients with postoperative pain and chronic pain due to cancer. (1981)

Heroin hydrochloride is approximately twice as potent as morphine sulfate, and acts slightly faster but for a shorter duration than morphine. Although patients with chronic pain due to advanced cancer differ from cancer patients with postoperative pain in terms of their degree of tolerance to the analgesic effects of morphine and heroin and their reports of various elements of mood, there is, thus far, no indication that heroin has any unique advantage over morphine in terms of side effect occurrence or effects on mood at equianalgesic doses. Both drugs improve mood provided they are administered in doses which result in analgesia. While there appears to be some slight difference in the spectrum of side effects observed after heroin as compared to morphine, heroin and morphine share the most common side effects. The incidence of side effects following both drugs appear to be highest among those effects which are primarily somatic and undesirable. The use of visual analog scales concurrent with categorical pain and pain relief scores provides a means for the finer estimation of relative analgesic potency and time action. The results of these studies are in general agreement with those of other investigators. Where apparent differences exist they can usually be explained on the bases of differences in methods and subject populations.
Bromate Reduction by Iron(II) during Managed Aquifer Recharge: A Laboratory-Scale Study (2018)

The removal of bromate (BrO3−) as a byproduct of ozonation in subsequent managed aquifer recharge (MAR) systems has so far gained little attention. This preliminary study with anoxic batch experiments was executed to explore the feasibility of chemical BrO3− reduction in Fe-reducing zones of MAR systems and to estimate potential inhibition by NO3−. Results show that the reaction rate was affected by initial Fe2+/BrO3− ratios and by pH. The pH dropped significantly due to the hydrolysis of Fe3+ to hydrous ferric oxide (HFO) flocs. These HFO flocs were found to adsorb Fe2+, especially at high Fe2+/BrO3− ratios, whereas at low Fe2+/BrO3− ratios, the mass sum loss of BrO3− and Br− indicated intermediate species formation. Under MAR conditions with relatively low BrO3− and Fe2+ concentrations, BrO3− can be reduced by naturally occurring Fe2+, as the extensive retention time in MAR systems will compensate for the slow reaction kinetics of low BrO3− and Fe2+ concentrations. Under specific flow conditions, Fe2+ and NO3− may co-occur during MAR, but NO3− hardly competes with BrO3−, since Fe2+ prefers BrO3− over NO3−. However, it was found that when NO3− concentration exceeds BrO3− concentration by multiple orders of magnitude, NO3− may slightly inhibit BrO3− reduction by Fe2+.
Service-Learning Projects in Core Undergraduate Engineering Courses (2008)

The College of Engineering at the University of Massachusetts Lowell (UML) has integrated service-learning (S-L) into many of its core required undergraduate courses over the last three years. Projects that meet real community needs and that help students achieve academic objectives in these core courses are percieved to be difficult to create, but, in this paper, projects for 35 different undergraduate required courses are summarized to help faculty, staff, and students develop S-L projects for their own courses. Faculty at UML were encouraged to “start small rather than not at all.” Courses and projects include, for example, a first-year introduction to engineering course in which 340 students, divided into teams, designed and built moving displays illustrating various technologies for 60,000 middle school students that every year visit a history center that is part of a national park. Another example is a sophomore kinematics course in which student teams visited local playgrounds to assess their safety using deceleration, force, and impact equations learned from the course. Junior heat transfer courses focused in analyzing heat loss and making suggestions for heating system savings for a local food pantry, a city hall building, and a community mental health center, as well as for the university itself; these analyses were developed and presented to the stakeholders. Sophomore student teams from the materials course presented findings to the staff of a local textile history museum to help it begin updating its displays on recent developments in materials. Junior fluids, junior circuits, senior microprocessor, senior design of machine elements, and senior capstone design are having students design and build various parts of an automated canal lock opener for a local national park. Many of the projects are low-cost and can be implemented by individual faculty members without the requirement of a formal institutional program. These S-L projects are integrated into a wide variety of core courses (and not just design courses) and represent typically from 10 to 20 percent of the grade.
In Vitro Biomineralization Induced by Self-Assembled Extracellular Matrix Proteins (2007)

Extracellular matrix (ECM) proteins play an essential role during biomineralization in bone and engineered tissues. In a previous study [1], we showed that calcite preferentially nucleated on pure elastin fibers. However, the actual cellular ECM fibers are composed of a combination of proteins, primarily collagen, fibronectin and some elastin. Here we follow the calcium carbonate- and calcium phosphate- mineralization process in vitro when these ECM proteins are combined and determine the differences between these proteins in the biomineralization process. The surface morphology and mechanical properties of the protein fibers during the early stages were probed by atomic force microscopy (AFM) and shear modulation force microscopy (SMFM). The nucleation of the mineral crystals on the protein matrices was investigated by scanning electron microscopy (SEM). Preliminary data showed that the moduli of all protein fibers increased at the early stages, with collagen having the largest increase in supersaturated calcium bicarbonate solution. In metastable calcium phosphate solutions the modulus of the mixed elastin-fibronectin fibres increased to a greater extent than the moduli of the fibers composed of the single proteins. Longer exposure in the mineral solutions led to the formation of crystals templated along the self-assembled fiber structures.
Adenosine A2A receptor modulates vascular response in soluble epoxide hydrolase‐null mice through cyp2j‐epoxygenases and PPARγ (2013)

The interaction between adenosine and sEH in vascular response is not known. Therefore, we hypothesized that lack of sEH enhances adenosine‐induced relaxation through A 2A AR via cyp2j‐epoxygenases and PPARγ. sEH −/− showed an increase in A 2A AR (31%), cyp2j (65%) &amp; PPARγ (36%), and decrease in A 1 AR (30%) &amp; PPARα (27%) vs. sEH +/+ . NECA (adenosine analog), CGS 21680 (A 2A AR‐agonist) &amp; GW 7647 (PPARα‐agonist)‐induced responses were tested with L‐NAME (NO‐inhibitor), ZM‐241385, SCH‐58261 (A 2A AR‐antagonists), 14,15‐EEZE (EETs‐antagonist), AUDA, t‐ AUCB (sEH‐inhibitors) &amp; T0070907 (PPARγ‐antagonist). NECA‐induced relaxation was higher in sEH −/− (+12.94 ± 3.2%) vs. sEH +/+ (−5.35 ± 5.2%), that was blocked by ZM‐241385 (−22.42 ± 1.9%) &amp; SCH‐58261(−30.04 ± 4.2%). CGS‐21680‐induced relaxation was higher in sEH −/− (+37.4 ± 5.4%) vs. sEH +/+ (+2.14 ± 2.8%), that was not blocked by L‐NAME (p&gt;;0.05), whereas 14,15‐EEZE did (p&lt;0.05). Also, AUDA &amp; t‐AUCB did not change CGS‐21680‐induced response in sEH −/− (p&gt;;0.05), but reversed in sEH +/+ (AUDA: +45.33±4.1%, t ‐AUCB: +63.37±7.2). GW 7647 did not relax vs. CGS 21680 in sEH −/− (p&lt;0.05), and T0070907 blocked CGS 21680 induced relaxation in sEH −/− (+9.40 ± 3.1). These data suggest that A 2A AR‐induced relaxation in sEH −/− may depend on the up‐regulation of cyp2j , PPARγ and down‐regulation of A 1 AR, PPARα. Supported (BGF‐WVU, STF‐WVU, HL027339 , HL094447 , GM31278 &amp; z01 ES025034 ).
Predicting Clinical Benefit in Non-Small-Cell Lung Cancer Patients Treated with Epidermal Growth Factor Tyrosine Kinase Inhibitors (2005)

Erlotinib and gefitinib are small-molecule inhibitors of the epidermal growth factor tyrosine kinase. Erlotinib is approved for the treatment of locally advanced or metastatic non-small-cell lung cancer after failure of at least one prior chemotherapy regimen. Although it is active in unselected patients, clinical characteristics and tumor molecular markers associated with enhanced benefit have been identified. Notably, never-smoker status or a positive EGFR FISH test has been consistently predictive of greater erlotinib benefit. Other markers, such as EGFR mutations and EGFR protein expression, as determined by immunohistochemistry, and KRAS mutation status have not proven to be consistently associated with differential benefit.