gebhart/patrepeval huggingface dataset:
Effect of stimulation of natural killer cells with an anti-CD137 mAb on the efficacy of trastuzumab, cetuximab, and rituximab. (2012)

2514 Background: Antibody-dependent cell-mediated cytotoxicity (ADCC), mediated by natural killer (NK) cells, plays an important role in the efficacy of monoclonal antibodies (mAb)s. CD137 is a costimulatory molecule expressed on immune cells following activation, including NK cells. We hypothesize that as the antitumor efficacy of mAbs is due to ADCC, their activity can be enhanced by stimulation of NK cells with an anti-CD137 agonistic mAb. Methods: Upregulation of CD137 on NK cells was assessed using CD20+lymphoma, HER2+breast, and EGFR+head and neck cell lines and primary patient samples. NK cell degranulation, cytokine release and cytotoxicity were assessed by CD107a mobilization, IFN-γ secretion, and chromium release. Mechanism of synergy was explored by cell depletion in an immune competent mouse model. Xenotransplanted models were used to demonstrate anti-tumor activity and sufficiency of an innate immune response. Results: NK cells in human primary patient samples do not express CD137 at baseline, however CD137 is highly upregulated when encountering mAb-coated tumor cells. MAb-induced NK cell degranulation and cytotoxicity are enhanced by anti-CD137 agonistic mAb. In a murine lymphoma model, anti-CD137 mAb significantly enhances anti-tumor activity of anti-CD20 mAb leading to complete tumor resolution and prolonged survival. NK cell depletion completely abrogates the therapeutic effect. In seven xenotransplant models, sequential administration of rituximab, trastuzumab or cetuximab plus anti-CD137 mAb provided superior reduction in tumor burden and prolonged overall survival. In a phase 0 biomarker study, level of CD137 expression on circulating and intratumoral NK cells was influenced by disease burden, prior treatment, FcγRIII polymorphism, and time since mAb therapy. Conclusions: Our results demonstrate the synergy of anti-CD137 mAb and a tumor-targeting mAb by stimulation of mAb-activated NK cells with anti-CD137 mAb to enhance ADCC. These results support a novel, sequential antibody approach against CD20+B cell, HER2+breast, and EGFR+head and neck malignancies by targeting first the tumor and then the host immune system.
A functional chimeric DNA primase: the Cys4 zinc-binding domain of bacteriophage T3 primase fused to the helicase of bacteriophage T7. (1994)

Two colinear bacteriophage T7 gene 4 proteins provide helicase and primase functions in vivo. T7 primase differs from T7 helicase by an additional 63 residues at the amino terminus. This terminal domain contains a zinc-binding motif which mediates an interaction with the basic primase recognition sequence 3'-CTG-5'. We have generated a chimeric primase in which the 81 amino-terminal residues are derived from the primase of phage T3 and the 484 carboxyl-terminal residues are those of phage T7 helicase. The amino-terminal domain of T3 primase is 50% homologous with that of T7 primase. The resulting T3/T7 chimeric protein is a functional primase in vivo. While the primase activity of the purified protein is about one-third that of T7 primase, the recognition sites used and the oligoribonucleotides synthesized from these sites are identical. We conclude that the residues responsible for the interaction with the sequence 3'-CTG-5' are conserved between the chimeric and T7 proteins.
An asynchronous power aware and adaptive NoC based circuit (2008)

A fully power aware globally asynchronous locally synchronous network-on-chip circuit is presented in this paper. The circuit is arranged around an asynchronous network-on-chip providing a 17 Gbits/s throughput and automatically reducing its power consumption by activity detection. Both dynamic and static power consumptions are globally reduced using adaptive design techniques applied locally for each NoC units. The dynamic power consumption can be reduced up to a factor of 8 while the static power consumption is reduced by 2 decades in stand-by mode.
Branched structures in the intracellular DNA of herpes simplex virus type 1 (1996)

Herpes simplex virus type 1 (HSV-1) replication produces large intracellular DNA molecules that appear to be in a head-to-tail concatemeric arrangement. We have previously suggested (A. Severini, A.R. Morgan, D.R. Tovell, and D.L.J. Tyrrell, Virology 200:428-435, 1994) that these DNA species may have a complex branched structure. We now provide direct evidence for the presence of branches in the high-molecular-weight DNA produced during HSV-1 replication. On neutral agarose two-dimensional gel electrophoresis, a technique that allows separation of branched restriction fragments from linear fragments, intracellular HSV-1 DNA produces arches characteristic of Y junctions (such as replication forks) and X junctions (such as merging replication forks or recombination intermediates). Branched structures were resolved by T7 phage endonuclease I (gene 3 endonuclease), an enzyme that specifically linearizes Y and X structures. Resolution was detected by the disappearance of the arches on two-dimensional gel electrophoresis. Branched structures were also visualized by electron microscopy. Molecules with a single Y junction were observed, as well as large tangles containing two or more consecutive Y junctions. We had previously shown that a restriction enzyme which cuts the HSV-1 genome once does not resolve the large structure of HSV-1 intracellular DNA on pulsed-field gel electrophoresis. We have confirmed that result by using sucrose gradient sedimentation, in which both undigested and digested replicative intermediates sediment to the bottom of the gradient. Taken together, our experiments show that the intracellular HSV-1 DNA is held together in a large complex by frequent branches that create a network of replicating molecules. The fact that most of these branches are Y structures suggests that the network is held together by frequent replication forks and that it resembles the replicative intermediates of bacteriophage T4. Our findings add complexity to the simple model of rolling-circle DNA replication, and they pose interesting questions as to how the network is formed and how it is resolved for packaging into progeny virions.
Nosocomial pneumonia in adults: practical recommendations on diagnosis, treatment and prevention. Medical supplementation (2005)

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In situ Raman Spectroscopy of COOH-functionalized SWCNTs Trapped with Optoelectronic Tweezers (2021)

Abstract not provided
Venn diagrams in cardiovascular disease: the Heart Team concept (2013)

Venn diagrams are illustrations composed of overlapping circles that demonstrate the relations between finite collections of things1 and are most useful in defining areas of commonality among different aggregations. Originally described by John Venn in the 1880s to teach elementary set theory, these diagrams are most often used to illustrate set relationships in such fields as probability, statistics and computer science.

Venn diagrams can also be useful for understanding the roles of various stakeholders in the management of cardiovascular disease from its diagnosis through its treatment. As the field progresses, the area of overlap of the cardiovascular disease Venn diagram continues to expand. This is evident in many aspects of cardiovascular disease management, including individual diagnosticians and treatment specialists, diseases, technologies, institutions, payers and regulators. Despite a movement towards convergence in areas of disease management, however, professional societies remain in their individual silos. This article explores whether Venn diagrams of professional societies, which traditionally had little overlap or mutual engagement, should continue to converge until they merge into one.

The well-recognized concept of atherosclerosis as a disease that affects all vascular beds has focused therapeutic strategies on the coexistence, for example, of coronary artery disease and peripheral arterial disease in the same patient. Whereas in the past there was a tendency to treat an acute coronary syndrome as an isolated event in a patient, attention now focuses on the fact that other manifestations of the disease, such as peripheral arterial disease and cerebral vascular disease, are likely to be present in this patient as well, and the involvement of these other vascular beds may affect treatment strategies. Thus, the evolution of the understanding about atherosclerosis has stimulated physicians and surgeons who focus on these different vascular beds to strategize together about the treatment of this patient.

Another example of …
Mesogen exhibiting a Ch–A*–A phase sequence, a liquid-crystalline analogue of the Abrikosov phase (1991)

A number of optically active liquid-crystalline compounds have been prepared that have a chlorine atom attached to their asymmetric centres. Many of these materials exhibit unusual properties at their transitions to the liquid state. In this article we report the properties of one of these compounds: S-2-chloro-4-methylpentyl 4′-(4″-n-nonyloxybenzoyloxy)biphenyl-4-carboxylate. From thermal and optical studies it appears that this material undergoes a transition from a cholesteric phase to a smectic A phase via an intermediary twisted phase. The intermediary A* phase is belived to have a structure where there is helical ordering of the molecules occurring in the planes of the molecular layers. Theoretical models suggest that this twist is effected by the inclusion of screw dislocations in the structure of the phase in the form of a lattice of defects. This lattice is thought to be similar in nature to the Abrikosov flux lattice found in superconductors.
Spectroscopy and gain measurements of Nd^3+ in SrF_2 and other fluorite-structure hosts (1991)

We investigate the optical properties of Nd3+ in CaF2, SrF2, and BaF2 with the intent of determining whether any of these materials might usefully serve as a laser-pumped-amplifier medium. The Nd3+ impurities tend to cluster at low levels of doping in CaF2, leading to the formation of nonluminescent centers. The addition of La or Y buffer ions to CaF2:Nd serves to increase the luminescent yield, but it also renders the system spectrally inhomogeneous. Although single-ion centers predominate in BaF2, the interstitial fluoride compensator occurs at the next-nearest-neighbor position relative to Nd3+, leading to unsuitably low transition strengths. The interstitial fluoride occurs at the nearest-neighbor site of Nd3+ in SrF2 and thereby induces significant oscillator strength into the 4f–4f transitions by breaking the inversion symmetry. The radiative lifetime of SrF2:Nd is found to be 1470 μsec by measuring the emission lifetime and quantum efficiency; this value was confirmed by Judd–Ofelt analysis of the absorption features. The peak-emission cross section at room temperature was determined to be 1.7 × 10−20 cm at 1036.5 nm. A maximum of 0.20 at. % Nd3+ may be doped into SrF2 without the occurrence of significant Nd clustering. Direct measurements of the gain spectrum in SrF2:Nd reveal the presence of the 4F3/2 → 2G9/2 excited-state absorption, although its effect on the emission cross section is only minor.
Somatic genomic landscape of over 15,000 patients with advanced-stage cancer from clinical next-generation sequencing analysis of circulating tumor DNA. (2016)

LBA11501 The full, final text of this abstract will be available at abstracts.asco.org at 7:30 AM (EDT) on Saturday, June 4, 2016, and in the Annual Meeting Proceedings online supplement to the June 20, 2016, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Editorial: The Covid-19 pandemic: when will it be under control? (2021)

status: Accepted
Faulting and crater development controlled by pre-existing topography - evidence from drone and satellite observations during the 2021 Cumbre Vieja eruption (2022)

&amp;lt;p&amp;gt;Volcanic terrains host complex and commonly steep morphologies and are often also subject to tensile and shear faulting episodes. Previous studies demonstrated that strike slip and dip slip faults deflect at topographic highs and may locally diverge to develop multiple fault branches with varying strike and dip directions. Although fault deflection is associated with dike-related faults, a direct link to the positioning of eruption craters could not be established yet. Here we show that the Cumbre Vieja eruptions occurred in a complex pre-existing topographic and structural environment that affected fault development and evolution of eruption vents.&amp;amp;#160;&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;We investigate available satellite radar data from the CosmoSkymed and TerraSAR-X missions, to track the temporal and spatial evolution of summit craters and faults. We find that summit craters are closely aligned in a direction NW-SE and developing a nested structure. We also conducted repeat drone measurements to acquire close-range optical images of the summit and nearby flanks. Results allow an in-depth analysis of the morphology of craters and the geometry, traces and throws of faults. We find that in late stages of the eruption important tensile faults evolve, and deflect at pre-existing topographic highs. We further find that these faults are developing complex sinkholes and secondary features due to their burial by loose unconsolidated material (i.e. tephra), and that the faults converge again at topographic lows, with varying degrees of the slip or dilation tendency. We discuss the coalignment of these structures with crater alignments, and present results from analogue models aiming to better constrain the varying deflection of faults controlled by topography.&amp;lt;/p&amp;gt;
PrimerBank: a resource of human and mouse PCR primer pairs for gene expression detection and quantification (2009)

PrimerBank (http://pga.mgh.harvard.edu/primerbank/) is a public resource for the retrieval of human and mouse primer pairs for gene expression analysis by PCR and Quantitative PCR (QPCR). A total of 306,800 primers covering most known human and mouse genes can be accessed from the PrimerBank database, together with information on these primers such as T(m), location on the transcript and amplicon size. For each gene, at least one primer pair has been designed and in many cases alternative primer pairs exist. Primers have been designed to work under the same PCR conditions, thus facilitating high-throughput QPCR. There are several ways to search for primers for the gene(s) of interest, such as by: GenBank accession number, NCBI protein accession number, NCBI gene ID, PrimerBank ID, NCBI gene symbol or gene description (keyword). In all, 26,855 primer pairs covering most known mouse genes have been experimentally validated by QPCR, agarose gel analysis, sequencing and BLAST, and all validation data can be freely accessed from the PrimerBank web site.
Approaches to the Sequence Determination of SV40 DNA (1974)

In recent years much attention has been focused on SV40. Indeed, not only can it be considered as a model system for the study of a small DNA virus growing in primate cells, but moreover, its oncogenic potential has been demonstrated in a variety of cells. Important information is already available concerning the molecular biology of SV40, e.g., regarding DNA replication, transcription pattern and the nature of several gene products. Ultimately, however, these biological properties will have to be explained on the basis of the chemical structure of the genome, even more so as several regions of genetic information are presumably not translated into proteins and some small regions may not even be transcribed in vivo.
Development of long-term cell lines and lymphoid clones reactive against murine and human tumors: a new approach to the adoptive immunotherapy of cancer. (1982)

We have investigated the use of T-cell growth factor (TCGF) to isolate and grow, in long-term culture, lymphoid cells with immunologic reactivity directed against syngeneic murine and autologous human tumors. Splenocytes from mice immune to a methylcholanthrene-induced sarcoma were expanded in TCGF, both before and after in vitro mixed lymphocyte-tumor cultures, and expressed high levels of cytotoxicity for fresh syngeneic solid tumor cells. Cloned lines have been isolated with a high level of specific lysis for the immunizing tumor. Similar studies of cytotoxic reactivity to a syngeneic FBL-3 lymphoma have given rise to long-term cytotoxic cell lines growing in TCGF capable of curing mice with disseminated lymphoma in adoptive transfer studies. Exposure to TCGF, of human peripheral lymphoid cells from cancer-bearing patients, results in the development of cytotoxicity to autologous fresh tumor. We have used clonal analysis by limiting dilution techniques to isolate individual cloned cells with this autologous antitumor reactivity. Infusion to autologous cytotoxic cells expanded 10,000-fold in TCGF and labeled with 111In into three cancer patients resulted in cell localization initially to the lung and subsequently to the liver and spleen. The application of these techniques for the cloning and expansion of antitumor T-lymphoid cells in TCGF has offered a new approach to adoptive immunotherapy.
Design, Synthesis, and Structure−Activity Relationships of Novel Insulin Receptor Tyrosine Kinase Activators (2008)

A novel series of symmetrical ureas of [(7-amino(2-naphthyl))sulfonyl]phenylamines were designed, synthesized, and tested for their ability to increase glucose transport in mouse 3T3-L1 adipocytes, a surrogate readout for activation of the insulin receptor (IR) tyrosine kinase (IRTK). A structure-activity relationship was established that indicated glucose transport activity was dependent on the presence of two acidic functionalities, two sulfonamide linkages, and a central urea or 2-imidazolidinone core. Compound 30 was identified as a potent and selective IRTK activator. At low concentrations, 30 was able to increase the tyrosine phosphorylation of the IR stimulated by submaximal insulin. At higher concentrations, 30 was able to increase tyrosine the phosphorylation levels of the IR in the absence of insulin. When administered intraperitoneally (ip) and orally (po), 30 improved glucose tolerance in hypoinsulinemic, streptozotocin-treated rats. These data provide pharmacological validation that small molecule IRTK activators represent a potential new class of antidiabetic agents.
Neural Greedy Pursuit for Feature Selection (2022)

We propose a greedy algorithm to select $N$ important features among $P$ input features for a non-linear prediction problem. The features are selected one by one sequentially, in an iterative loss minimization procedure. We use neural networks as predictors in the algorithm to compute the loss and hence, we refer to our method as neural greedy pursuit (NGP). NGP is efficient in selecting $N$ features when $N \ll P$, and it provides a notion of feature importance in a descending order following the sequential selection procedure. We experimentally show that NGP provides better performance than several feature selection methods such as DeepLIFT and Drop-one-out loss. In addition, we experimentally show a phase transition behavior in which perfect selection of all $N$ features without false positives is possible when the training data size exceeds a threshold.
Ublituximab (TGTX-1101), a Novel, Third-Generation Anti-CD20 Antibody Demonstrates Enhanced Antitumor Activity Compared to Rituximab in Primary CNS and Intraocular Lymphoma Murine Models. (2012)

Abstract Abstract 2755 Background: Primary Central Nervous lymphomas (PCNSL), that comprise primary cerebral lymphoma (PCL) and primary intraocular lymphoma (PIOL), are typically CD20+ diffuse large B-cell lymphomas that have no detectable disease outside the brain or eye. Rituximab (RTX), an anti-CD20 antibody, has demonstrated encouraging clinical benefit in systemic B-cell lymphomas as well as PCL and PIOL, however, the role of RTX in treatment of PCNSL/PIOL remains controversial, and these highly aggressive malignancies are often incurable with available therapies. Therefore, additional treatment options are needed. Ublituximab (UTX) is a novel, glycoengineered chimeric anti-CD20 monoclonal antibody (mAb) that has a high affinity for FcγRIIIa (CD16) receptors, and therefore greater ADCC activity than RTX (Le Garff-Tavernier et al., 2011). Herein, we assess the antitumor effects of UTX compared to RTX in murine models of PCL and PIOL. Methods: The murine lymphoma B-cell line A20.IIA-GFP-hCD20 (H-2d) was injected into the right cerebral striatum (PCL model) or the vitreous (PIOL model) of adult BALB/c mice (H-2d); 7 days later, single doses of UTX were injected either into the tumor site intracerebrally (PCL) or intravitreously (PIOL), or at distance of the tumor site (intrathecally, PCL). RTX was used as a reference compound. Survival was monitored for injected mice for up to 100 days, and flow cytometric analyses were performed to assess tumor growth and T-cell infiltration. Results: In PCL and PIOL models, single doses of UTX had a marked antitumor effect more pronounced than that obtained with an equivalent dose of RTX. In the PCL model, there was an overall survival (OS) advantage with intracerebral injections of UTX compared to RTX (50% vs. 10%, n=10 in each group, p=0.0028). The reduction in tumor cells was correlated with an increased proportion of CD8+ T cells. Moreover, intrathecal injections of UTX increased OS compared to buffer solution. In the PIOL model, the absolute number of tumor cells analyzed 8 days after treatment had decreased more significantly (p=0.027) with UTX compared to the RTX group. This finding again confirmed the superiority of UTX in this setting. Conclusions: These results confirm that the novel, third-generation mAb, UTX has a sustained and greater antitumor effect than RTX on primary cerebral and intraocular lymphomas when assessed in vivo. Additional experiments evaluating the combination of UTX + methotrexate are ongoing. Clinical trials to evaluate UTX as an innovative therapeutic approach to treat primary cerebral and intraocular B-cell lymphomas are currently being evaluated. Disclosures: Jacquet: LFB Biotechnologies: Employment. Fridman:LFB Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Sportelli:TG Therapeutics, Inc.: Employment, Equity Ownership. Urbain:LFB Biotechnologies: Employment.
Novel antibiotics napyradiomycins. Production, isolation, physico-chemical properties and biological activity. (1986)

Novel antibacterial antibiotics napyradiomycins A, B1, B2, B3, C1 and C2 have been isolated from the culture broth of Chainia rubra MG802-AF1. In this paper, taxonomy of the producer, and production, isolation, physico-chemical properties and biological activities of napyradiomycins are reported. They contain the naphtopyran chromophore and halogens, and inhibit the growth of Gram-positive bacteria including drug-resistant strains.
SR Replication Segment for Multi-point Service Delivery (1998)

This document describes the SR Replication segment for multi-point
service delivery. A SR Replication segment allows a packet to be
replicated from a replication node to downstream nodes.