gebhart/patrepeval huggingface dataset:
Abstract DDT02-01: FAP-4-1BBL: A next generation, targeted costimulatory agonist for cancer immunotherapy (2018)

Abstract This talk will describe a new drug candidate for cancer immunotherapy, FAP-4-1BBL, a next generation, tissue-targeted agonist of the 4-1BB costimulatory receptor. Agonizing 4-1BB to enhance the activity of antitumor T cells has been successfully exploited by 2nd and 3rd generation CAR T-cell therapies for hematological malignancies. However, the clinical development of first-generation, 4-1BB agonistic antibodies for systemic administration has been hampered by significant hepatic toxicity. Here we describe a next generation, fibroblast activated protein (FAP)-targeted 4-1BB agonist whose activity is independent of Fc-gamma-receptor (FcγR)-binding, is safe in preclinical models (including non-human primates using doses of up to 50 mg/kg) and is significantly more potent and efficacious than first generation, standard 4-1BB agonistic antibodies when compared side-by-side in preclinical models. In preclinical models, combination of FAP-4-1BBL with T-cell bispecific antibodies leads to significant increases in T cell infiltration into the tumor, CD8/Treg ratio and anti-tumoral efficacy. We conclude that the tumor-targeted cross-linking of 4-1BB provides a safe and effective way for co-stimulation of T cells for cancer immunotherapy and its combination with T-cell bispecific antibodies may provide a convenient “off-the-shelf,” systemic cancer immunotherapy approach for many tumor types. Citation Format: Pablo Umana. FAP-4-1BBL: A next generation, targeted costimulatory agonist for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr DDT02-01.
Supplementary Figure 1 from Local Delivery of lnterleukin-12 Using T Cells Targeting VEGF Receptor-2 Eradicates Multiple Vascularized Tumors in Mice (2023)

&lt;p&gt;PDF file - 365K&lt;/p&gt;
Adaptive Control of a Sliding Seat Using Magnetorheological Energy Absorbers (2010)

Feasibility of a sliding seat utilizing adaptive control of a magnetorheological (MR) energy absorber (MREA) to minimize loads imparted to a payload mass in a ground vehicle for frontal impact speeds as high as 7 m/s (15.7 mph) is investigated. The crash pulse for a given impact speed was assumed to be a rectangular deceleration pulse having a prescribed magnitude and duration. The adaptive control objective is to bring the payload (occupant plus seat) mass to a stop using the available stroke, while simultaneously accommodating changes in impact velocity and occupant mass ranging from a 5th percentile female to a 95th percentile male. The payload is first treated as a single-degree-of-freedom (SDOF) rigid lumped mass, and two adaptive control algorithms are developed: (1) constant Bingham number control, and (2) constant force control. To explore the effects of occupant compliance on adaptive controller performance, a multi-degree-of-freedom (MDOF) lumped mass biodynamic occupant model was integrated with the seat mass. The same controllers were used for both the SDOF and MDOF cases based on SDOF controller analysis because the biodynamic degrees of freedom are neither controllable nor observable. The designed adaptive controllers successfully controlled load-stroke profiles to bring payload mass to rest in the available stroke and reduced payload decelerations. Analysis showed extensive coupling between the seat structures and occupant biodynamic response, although minor adjustments to the control gains enabled full use of the available stroke.
Solutal‐Marangoni‐Flow‐Mediated Growth of Patterned Highly Crystalline Organic Semiconductor Thin Film Via Gap‐Controlled Bar Coating (2021)

Abstract Application‐oriented patterned growth of organic semiconductor (OSC) thin films with single crystalline domains is crucial for fabricating sophisticated high‐performance organic‐electronic and optoelectronic devices; however, fabricating these patterned nanometer‐thick crystals in a simple, fast, and effective manner is a difficult task with a roll‐to‐roll printing process. Here, a simple bar‐coating approach to form an array of single‐crystal‐like OSC thin‐film patterns at a rate of a few millimeters per second is introduced. To this end, the processing parameters of a gap‐controlled bar‐coating method is optimized, including coating speed, crystal nucleation, and solution fluidics, which allow a high degree of morphological control of bar‐coated OSC films in an area of several centimeters. In particular, it is demonstrated that the solutal‐Marangoni flow induced by a suitable solvent additive can considerably improve molecular mass transport and induce favorable vertical phase separation. Thus, organic transistors based on the OSC patterns fabricated with the additive‐assisted bar coating show a field‐effect mobility of up to 20 cm 2 V −1 s −1 and superior operational stability. The proposed bar coating method will facilitate an industry‐level application of organic electronics.
Prostaglandin D2 metabolite in urine is an index of food allergy (2017)

Food allergy is immediate hypersensitive reactions to ingested foods. Since early diagnosis is effective for disease control, development of an objective diagnostic index is required. Using mediator-lipidomics, we found that levels of the urinary prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) metabolite, tetranor-PGDM, reflected the severity of the allergic symptoms and intestinal mast cell hyperplasia in mice. Repeated oral challenges with ovalbumin promoted allergic symptoms in sensitized mice. Particularly, the allergic mice presented with increased numbers of intestinal mast cells, which strongly expressed hematopoietic PGD synthase (H-PGDS). The levels of urinary tetranor-PGDM increased as the disease progressed. Treatment with a mast cell inactivator or an anti-inflammatory steroid attenuated these symptoms and decreased the tetranor-PGDM urinary levels. The levels of urinary tetranor-PGDM did not correlate with the disease severity in murine models of colitis, asthma, or allergic dermatitis. Furthermore, we have shown that urinary levels of tetranor-PGDM were significantly higher in patients with food allergy than those in healthy volunteers and patients with other types of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. These findings suggest that urinary tetranor-PGDM is a useful diagnostic index of food allergy in both mice and humans.
Src kinase activation by direct interaction with the integrin β cytoplasmic domain (2003)

Src tyrosine kinases transmit integrin-dependent signals pivotal for cell movement and proliferation. Here, we establish a mechanism for Src activation by integrins. c-Src is shown to bind constitutively and selectively to beta3 integrins through an interaction involving the c-Src SH3 domain and the carboxyl-terminal region of the beta3 cytoplasmic tail. Clustering of beta3 integrins in vivo activates c-Src and induces phosphorylation of Tyr-418 in the c-Src activation loop, a reaction essential for adhesion-dependent phosphorylation of Syk, a c-Src substrate. Unlike c-Src, Hck, Lyn, and c-Yes bind more generally to beta1A, beta2, and beta3 cytoplasmic tails. These results invoke a model whereby Src is primed for activation by direct interaction with an integrin beta tail, and integrin clustering stabilizes activated Src by inducing intermolecular autophosphorylation. The data provide a paradigm for integrin regulation of Src and a molecular basis for the similar functional defects of osteoclasts or platelets from mice lacking beta3 integrins or c-Src.
Jasmonate-independent regulation of digestive enzyme activity in the carnivorous butterwort Pinguicula × Tina (2020)

Carnivorous plants within the order Caryophyllales use jasmonates, a class of phytohormone, in the regulation of digestive enzyme activities. We used the carnivorous butterwort Pinguicula × Tina from the order Lamiales to investigate whether jasmonate signaling is a universal and ubiquitous signaling pathway that exists outside the order Caryophyllales. We measured the electrical signals, enzyme activities, and phytohormone tissue levels in response to prey capture. Mass spectrometry was used to identify proteins in the digestive secretion. We identified eight enzymes in the digestive secretion, many of which were previously found in other genera of carnivorous plants. Among them, alpha-amylase is unique in carnivorous plants. Enzymatic activities increased in response to prey capture; however, the tissue content of jasmonic acid and its isoleucine conjugate remained rather low in contrast to the jasmonate response to wounding. Enzyme activities did not increase in response to the exogenous application of jasmonic acid or coronatine. Whereas similar digestive enzymes were co-opted from plant defense mechanisms among carnivorous plants, the mode of their regulation differs. The butterwort has not co-opted jasmonate signaling for the induction of enzyme activities in response to prey capture. Moreover, the presence of alpha-amylase in digestive fluid of P. × Tina, which has not been found in other genera of carnivorous plants, might indicate that non-defense-related genes have also been co-opted for carnivory.
A MULTI FACETS COMPOSITE PANEL REFLECTARRAY ANTENNA FOR A SPACE CONTOURED BEAM ANTENNA IN KU BAND (2013)

A 1.3m piecewise re∞ectarray demonstrator has been designed, manufactured and tested, that radiates a contoured beam coverage over North America. A very good agreement is obtained between the theoretical and measured radiation patterns. Many innovative techniques and processes were developed in order to meet the challenging speciflcations of a space telecommunication antenna.
Improving Performance of Sparse Numerical Linear Algebra Computations (2010)

With new processor families appearing every few years, it is increasingly harder to achieve high performance rates in sparse matrix computations. This monograph studies new methods for sparse matrix factorizations and applies them efficiently while retaining ease of use of existing solutions. The implementations are timed and analyzed using a commonly accepted set of test matrices. Contemporary processors are used for the tests. The new factorization techniques are proven to be quite competitive with state of the art software. In addition, an optimization effort is applied to an iterative algorithm that stands out for its numerical robustness. This also gives satisfactory results on the tested computing platforms in terms of performance improvement. The same set of test matrices is used to enable an easy comparison between both investigated techniques, even though they are customarily treated separately in the literature. Possible extensions of the presented work range from easily conceivable merging with existing solutions to rather more evolved schemes dependent on hard to predict progress in theoretical and algorithmic research.
2-Position Base-Modified Analogues of Adenophostin A as High-Affinity Agonists of the d-myo-Inositol Trisphosphate Receptor:  In Vitro Evaluation and Molecular Modeling (2008)

Adenophostin A (AdA) is a potent agonist of the d-myo-inositol 1,4,5-trisphosphate receptor (Ins(1,4,5)P3R). Various 2-aminopurine analogues of AdA were synthesized, all of which (guanophostin 5, 2,6-diaminopurinophostin 6, 2-aminopurinophostin 7, and chlorophostin 8) are more potent than 2-methoxy-N6-methyl AdA, the only benchmark of this class. The 2-amino-6-chloropurine nucleoside 11, from Vorbrüggen condensation of 2-amino-6-chloropurine with appropriately protected disaccharide, served as the advanced common precursor for all the analogues. Alcoholysis provided the precursor for 5, ammonolysis at high temperature the precursor for 6, and ammonolysis under mild conditions the precursor for synthesis of 7 and 8. For 8, the debenzylation of precursor leaving the chlorine untouched was achieved by judicious use of BCl3. The reduced potency of chlorophostin 8 and higher potency of guanophostin 5 in assays of Ca2+ release via recombinant Ins(1,4,5)P3R are in agreement with our model suggesting a cation-pi interaction between AdA and Ins(1,4,5)P3R. The similar potencies of 2,6-diaminopurinophostin (6) and 2-aminopurinophostin (7) concur with previous reports that the 6-NH2 moiety contributes negligibly to the potency of AdA. Molecular modeling of the 2-amino derivatives suggests an interaction between the carboxylate side chain of Glu505 of the receptor and the 2-NH2 of the ligand, but for 2-methoxy-N6-methyl AdA the carboxylate group of Glu505 is deflected away from the methoxy group. A helix-dipole interaction between the 1-phosphate of Ins(1,4,5)P3 and the 2'-phosphate of AdA with alpha-helix 6 of Ins(1,4,5)P3R is postulated. The results support a proposed model for high-affinity binding of AdA to Ins(1,4,5)P3R.
Structure and Surface Morphology of Thermal SiO<sub>2</sub> Grown on 4H-SiC by Metal-Enhanced Oxidation Using Barium (2017)

Surface morphology and electrical properties of silicon dioxide (SiO 2 ) on 4H-SiC substrates formed by metal-enhanced oxidation (MEO) using barium (Ba) atoms were systematically investigated. It was found that severe surface roughening caused by Ba-MEO can be suppressed by using SiO 2 capping prior to MEO. The Ba atoms at the SiO 2 /SiC interface were found to diffuse to the oxide surface through the deposited SiO 2 capping layer, and then the Ba density reduced to ~10 14 cm -2 before stable MEO. The resulting SiO 2 /SiC interface showed the reduced interface state density but the insulating property of the oxides was significantly degraded.
Increasing the density of nanomedicines improves their ultrasound-mediated delivery to tumours (2015)

Nanomedicines have provided fresh impetus in the fight against cancer due to their selectivity and power. However, these agents are limited when delivered intravenously due to their rapid clearance from the bloodstream and poor passage from the bloodstream into target tumours. Here we describe a novel stealthing strategy which addresses both these limitations and thereby demonstrate that both the passive and mechanically-mediated tumour accumulation of the model nanomedicine adenovirus (Ad) can be substantially enhanced. In our strategy gold nanoparticles were thoroughly modified with 2kDa polyethyleneglycol (PEG) and then linked to Ad via a single reduction-cleavable 5kDa PEG. The resulting Ad-gold-PEG construct was compared to non-modified Ad or conventionally stealthed Ad-poly[N-(2-hydroxypropyl)methacrylamide] (Ad-PHPMA). Notably, although Ad-gold-PEG was of similar size and surface charge to Ad-PHPMA the increase in density, resulting from the inclusion of the gold nanoparticles, provided a substantial enhancement of ultrasound-mediated transport. In an in vitro tumour mimicking phantom, the level and distance of Ad-gold-PEG transport was shown to be substantially greater than achieved with Ad-PHPMA. In in vivo studies 0.1% of an unmodified Ad dose was shown to accumulate in tumours, whereas over 12% of the injected dose was recovered from the tumours of mice treated with Ad-gold-PEG and ultrasound. Ultimately, a significant increase in anti-tumour efficacy resulted from this strategy. This stealthing and density-increasing technology could ultimately enhance clinical utility of intravenously delivered nanoscale medicines including viruses, liposomes and antibodies.
Motoric impairment versus iron deposition gradient in the subthalamic nucleus in Parkinson’s disease (2020)

Advancing PD with more severe motor impairment leads to more iron deposition in the STN and adjacent WM, as shown in the QSM signal. Loss of the STN inner QSM signal gradient should be considered as an image marker for more severe motor impairment in PD patients.
Hypopharyngeal Squamous Cell Carcinoma: Treatment Results in 138 Consecutively Admitted Patients (2000)

The aim of this study was to evaluate the results of the initial and salvage treatment for hypopharyngeal carcinoma. The study was conducted in 1963 to 1991 and included 138 patients (38 females (28%) and 100 males (73%)). Most of the tumours originated in the piriform sinus (86%). Tumour stage distribution was T1: 20%, T2: 27%, T3: 37% and T4: 17% and nodal stage distribution was N0: 45%, N1: 25%, N2: 10%, and N3: 20%. Primary treatment was delivered with curative intent in 124 out of 138 cases (90%). Treatment failure was noted in 98 patients, with 55% recurrence in T-position, 39% in N-position, and 14% at distant metastases sites. Salvage surgery was successful in 9 out of 32 patients. The overall 5-year locoregional tumour control, cause-specific and overall survival rates were 20%, 25% and 19%, respectively. Univariate actuarial analysis showed that T- and N-stage, clinical stage, tumour size and well-differentiated tumours were significant prognostic parameters. A Cox multivariate analysis showed that only the T- and N-stages were independent prognostic factors. In conclusion, the prognosis for advanced hypopharyngeal carcinoma is extremely poor and the meagre results with conventional radiotherapy alone indicate that other treatment modalities should be introduced in the management of this disease.
ChemInform Abstract: POTENTIAL ANTITUMOR AGENTS. 39. ANILINO RING GEOMETRY OF AMSACRINE AND DERIVATIVES: RELATIONSHIP TO DNA BINDING AND ANTITUMOR ACTIVITY (1984)

Abstract Es werden die Verbindungen (V) hergesteUt und hinsichtlich ihrer Bindungsverhältnisse an DNA sowie der damit zusammenhängenden Antitumor‐Wirkung untersucht.
ChemInform Abstract: THE REACTION OF IMIDAZOLIDINE‐2‐THIONE WITH CARBON DISULFIDE (1981)

Abstract Imidazolidin‐2‐ thion (I) reagiert mit NaH/CS, in Gegenwart von Diethylcarbonat (wodurch die Ausb. erheblich verbessert wird) unter Bildung des Bis(carbothioxamido)‐ethans (II).
Isolating, Expanding, and Infecting Human and Rodent Fetal Neural Progenitor Cells (2008)

Neural progenitor cells have tremendous utility for understanding basic developmental processes, disease modeling, and therapeutic intervention. The protocols described in this unit provide detailed information to isolate and expand human and rodent neural progenitor cells in culture for several months as floating aggregates (termed neurospheres) or plated cultures. Detailed protocols for cryopreservation, neural differentiation, exogenous gene expression using lentivirus, and transplantation into the rodent nervous system are also described.
Quantitative Analysis of the Association Between Follow-Up Duration and Severity of Limbal Stem Cell Deficiency or Visual Acuity in Aniridia (2020)

We quantitatively demonstrate that LSCD severity and visual impairment significantly progress as follow-up duration increases.
Is the Pace of Biomedical Innovation Slowing? (2018)

The pace of biomedical innovation is important because it determines the rate of progress in medicine and allied disciplines. A review of the history of medical advances reveals that the three decades from 1950 to 1980 were a particularly innovative time. Subsequent decades have seen fewer seminal advances, despite continued improvements in many biomedical technologies. Although the biomedical sciences continue to be innovative, the question posed in this essay is whether the rate of innovation has slowed relative to the available knowledge base. The pace of innovation varies tremendously depending on the specific field considered. Overall, the pace of innovation may be slower than in the past, especially when measured against the biomedical knowledge base available today versus that available then. Ten factors are discussed that could be slowing biomedical innovation. If biomedical innovation is slowing, then restoring a faster pace would require the cooperation of government, industry and academia, for the problems are multifaceted and intertwined.
Surge snubber design for high power-density DC-DC converters in HVDC power distribution systems (2012)

In an isolated DC-DC converter utilized in the HVDC power distribution system, a large surge voltage occurs across the secondary-side diodes due to the transformer's leakage inductance, and then the diodes with a large withstand voltage are required. However, those diodes cause a lot of power loss. In this paper, a simple surge snubber with prominent surge suppression capability is examined, and the surge-voltage evaluation through the analysis using the high-frequency equivalent circuits, which is followed by the experimental confirmation. Furthermore, the the optimum design of its surge-snubber capacitor is presented.
The synthesis, characterization, and copolymerization of the macromonomer .alpha.-(p-phenyl glycidyl ether)-.omega.-chloropolyisobutylene (PGE-PIB). 2. The synthesis of PGE-PIB and its copolymerization with epichlorohydrin and ethylene oxide (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe synthesis, characterization, and copolymerization of the macromonomer .alpha.-(p-phenyl glycidyl ether)-.omega.-chloropolyisobutylene (PGE-PIB). 2. The synthesis of PGE-PIB and its copolymerization with epichlorohydrin and ethylene oxideJoseph P. Kennedy and J. D. CarterCite this: Macromolecules 1990, 23, 5, 1238–1243Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://doi.org/10.1021/ma00207a003RIGHTS & PERMISSIONSArticle Views157Altmetric-Citations7LEARN 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 InReddit PDF (490 KB) Get e-Alerts Get e-Alerts
Scaffold Design and Manufacturing: From Concept to Clinic (2009)

Since Robert Langer and colleagues pioneered the concept of reconstructing tissue using cells transplanted on synthetic polymer matrices in the early 1990s, research in the field of tissue engineering and regenerative medicine has exploded. This is especially true in the development of new materials and structures that serve as scaffolds for tissue reconstruction. The basic tenet of the last two decades holds scaffolds as degradable materials providing temporary function while enhancing tissue regeneration through the delivery of biologics. Although a number of new scaffolding materials and structures have been developed in research laboratories, the application of such materials practice even has been extremely limited. This paper argues that better integration of all these factors is needed to bring scaffolds from "concept to clinic". It reviews current work in all these areas and suggests where future work and funding is needed.