gebhart/patrepeval huggingface dataset:
Patient-reported outcomes (PROs) with ibrutinib-rituximab in Waldenström macroglobulinemia (WM): Results from iNNOVATE. (2019)

8018 Background: Anemia and fatigue can impair quality of life in patients (pts) with WM. Ibrutinib (ibr) as single agent or in combination with RTX is FDA-approved for WM. In pts with RTX-refractory WM, single-agent ibr induced meaningful improvements in PROs (Trotman, EHA 2017). In iNNOVATE, ibr-RTX (IR) produced higher rates of sustained hemoglobin improvement and meaningful improvements in PROs versus placebo-RTX (R; Dimopoulos NEJM 2018). Here, we report detailed PRO analyses from iNNOVATE. Methods: Pts with symptomatic WM requiring therapy were randomized to daily 420 mg oral ibr or placebo, both with RTX (375 mg/m 2 /week IV at weeks 1–4 and 17–20). PRO measures included FACIT-Fatigue (FACIT-F), FACT-An total score (TS) and anemia subscale score (AS), and EQ-5D-5L (EuroQol Research Foundation. EQ-5D is a trade mark of the EuroQol Research Foundation) visual analog scale (VAS), and utility score (US). Results: For 150 randomized pts (n=75/arm), most common reasons for initiating therapy were fatigue (61%), constitutional symptoms (32%), and anemia (32%). Baseline PRO scores were comparable in both arms. At a median follow-up of 26.5 mo, numerically more pts showed clinically meaningful improvement in FACIT-F, TS, and AS with IR than R (Table). Median time to PRO improvement was short (1-2 mo) in both arms. At week 25, the Pearson correlation coefficients were 0.28, 0.29, and 0.26 for changes in hemoglobin levels vs changes in FACIT-F, TS and AS, respectively, in the IR arm; no meaningful correlations were observed on R. The correlation coefficients were -0.32, -0.33, -0.35 and -0.26 for changes in IgM levels vs changes in FACIT-F, TS, AS, and EQ-VAS, respectively, for IR and 0.29 and 0.35 vs FACIT-F and TS for R. Conclusions: Clinical response and improvements in anemia with IR are consistent with more pts showing clinically meaningful improvement in PROs versus R. Changes in IgM correlate with improvements in PROs. Clinical trial information: NCT02165397. [Table: see text]
Abstract LB-185: Oxidative damage targets complexes containing DNA methyltransferases, SIRT1 and polycomb members to promoter CpG islands (2011)

Abstract A key question in cancer epigenetics is how cancers of multiple types simultaneously acquire global losses and gains of DNA methylation. The increases often occur in promoter CpG islands and can be associated with transcriptional inactivation of key tumor suppressor genes. Here we demonstrate a molecular response to oxidative damage, a key factor in cancer risk states, which could help explain the gains and losses of DNA methylation that occur during tumor progression. Within 30 minutes of exposing cells to the reactive oxygen species, hydrogen peroxide (H2O2), the major maintenance enzyme for DNA methylation, DNMT1, becomes notably more tightly bound to chromatin. Concomitantly, DNMT1 targets SIRT1 to chromatin and both proteins become part of a large multi-protein complex(es) which also contains the de novo DNA methyltransferase, DNMT3B. This oxidative damage-induced complex also contains specific polycomb group members, which, in the context of SIRT1, define the Polycomb Repressive Complex 4 (PRC4), previously found only in embryonic and adult stem cells and cancer cells. By examining chromatin on a genome-wide scale, we demonstrate that H2O2 treatment preferentially damages GC-rich regions of DNA. This damage causes a shift in localization of the above complex(es) from non-GC-rich to GC-rich regions of the genome including promoter CpG islands of which some are DNA hypermethylated in cancer cells. Additionally, this treatment causes a decrease in nascent RNA transcript levels of these genes that have oxidative damage-induced enrichment of the silencing complex in their CpG island-containing promoters. Thus, oxidative damage induces formation and localization of a silencing complex that may in part explain cancer specific aberrant losses and gains in DNA methylation associated with gene transcriptional silencing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-185. doi:10.1158/1538-7445.AM2011-LB-185
Investigation of Cerebral O-(2-[18F]Fluoroethyl)-L-Tyrosine Uptake in Rat Epilepsy Models (2020)

There was no evidence for increased cerebral [<sup>18</sup>F]FET uptake after epileptic seizures neither in the rat models nor in patients. The SE model even showed decreased [<sup>18</sup>F]FET uptake throughout the brain. We conclude that epileptic seizures per se do not cause a longer lasting increased [<sup>18</sup>F]FET accumulation and are unlikely to be a major cause of pitfall for brain tumor diagnostics.
Combined Study of Li2FeSiO4 Otained by Different Synthesis Routes (2009)

Abstract not Available.
Cellular pattern formation in circular domains (1997)

An analysis of stationary and nonstationary cellular patterns observed in premixed flames on a circular, porous plug burner is presented. A phenomenological model is introduced, that exhibits patterns similar to the experimental states. The primary modes of the model are combinations of Fourier-Bessel functions, whose radial parts have neighboring zeros. This observation explains several features of patterns, such as the existence of concentric rings of cells and the weak coupling between rings. Properties of rotating rings of cells, including the existence of modulated rotations and heteroclinic cycles can be deduced using mode coupling. For nonstationary patterns, the modal decomposition of experimental data can be carried out using the Karhunen-Loeve (KL) analysis. Experimental states are used to demonstrate the possibility of using KL analysis to differentiate between uniform and nonuniform rotations. The methodology can be extended to study more complicated nonstationary patterns. In particular, it is shown how the complexity of "hopping states" can be unraveled through the analysis. (c) 1997 American Institute of Physics.
A proposal of an off-line PACS based on a personal database (1991)

Problems with picture archiving and communication systems (PACS) are focused and an off-line PACS of practical value is proposed in this paper. This system is based on the personal database where each patient has his/her own recording medium. This medium files all medical information as well as images of value, and is carried with a patient through hospital. Advantages over the conventional or on-line PACS communicating through a network are discussed and a possibility of practical use is analysed showing a prototype system. The biggest advantage of this system is quick and easy access to the images of concern and a small amount of cost for initial investment. It is also pointed out that the format of the data recording on the disk has to be standardized so that this system could be used for a medical care system over a wide area.
Abstract 2161: Network-based inference of ALK oncogenic signaling in T-cell lymphoproliferative disorders (2010)

Abstract Anaplastic large cell lymphomas (ALCL) are a subset of T-cell Non-Hodgkin Lymphomas (T-NHL) in which the intracytoplasmic domain of the anaplastic lymphoma kinase (ALK) gene is frequently fused to nucleophosmin (NPM1). It has been previously shown that the transcription factor STAT3 is a major substrate of ALK enzymatic activity and it is strictly required for the growth and survival of ALK-transformed cells. With the aim to unravel the regulatory network underlying NPM-ALK-mediated transformation and tumor maintenance, we timely dissected the mRNA and miRNA expression signature of ALK-positive ALCL cell lines following ALK or STAT3 silencing. We observed that the majority of ALK-regulated genes were concordantly dependent on STAT3, including known and novel STAT3 target genes. Additional transcription factors (C/EBP beta, LEF1, and others) emerged as STAT3-dependent initiators and master regulators of ALK oncogenic properties in ALCL. However, STAT3 signaling was inconsistent and completely dispensable in non small cell cancer cell lines expressing EML4-ALK fusion proteins, suggesting a T-cell specific STAT3 regulatory network. Finally, we analyzed the gene expression profiling of 90 systemic peripheral T cell lymphomas, including a set of ALK positive and negative ALCL (n=36). We observed that ALK positive ALCL were significantly clustered in a separate subgroup, characterized by a relevant STAT3 signature. Using prediction analyses, we identified a set of genomic classifiers able to a clearly separate ALK positive and ALK negative ALCL from other T-NHL. In conclusion we proved that inference of ALK oncogenic transcriptional networks is a powerful tool to identify meaningful signaling molecules that regulate the transition into a pathologic cellular state. Our molecular classification suggests that ALCL may represent a unique entity discernible from other T-NHL, and that a restricted number of genes can be instrumental for clinical stratification and, possibly, to address the therapy of patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2161.
Expression of Fas Ligand in Activated T Cells Is Regulated by c-Myc (2000)

The transcription factor c-Myc is important for the control of cell cycle progression, neoplasia, and apoptotic cell death. c-Myc dimerizes with its partner Max to form an active transcription factor complex. Little is known, however, about the transcriptional targets of c-Myc and their roles in c-Myc-induced cell death. Here we demonstrate that T cell activation-induced expression of Fas ligand (FasL, CD95-L, APO-1-L), which can induce apoptotic cell death in many different cell types, is regulated by c-Myc. Down-modulation of c-Myc protein via antisense oligonucleotides blocked activation-induced FasL mRNA and protein expression and functional FasL expression in activated T cells and T cell lines. Further, FasL promoter activity in T cells is driven by overexpression of c-Myc and inhibited by expression of dominant-negative mutants of c-Myc and Max. Our findings indicate that c-Myc controls apoptotic cell death in T cells through regulation of FasL expression.
Numerical study on joint quantization and control under block-coding (2004)

This paper addresses the joint quantization and control problem for hidden Markov chains with variable-length block-coding. The aim is to understand the impact of communication bandwidth and information delay (due to block-coding) on the control performance. A heuristic algorithm is developed to solve the dynamic programming (DP) equation through the introduction of a metric on the discrete observation space. Numerical results are presented demonstrating the attention division in block-coding and the tradeoffs between control performance and communication bandwidth.
Ultrafast Dynamics of Band-Edge Photonic Crystals Lasers (2009)

Temporal characteristics of band-edge photonic crystal lasers were explored with high resolution up-conversion system. The InGaAs/InP photonic crystal laser operates at room temperature at 1.55 µm with temporal responses indicating modulation speeds greater than 25GHz
Organolanthanide-catalyzed dehydrogenative coupling of silanes. Mechanistic implications (1991)

Organolanthanide complexes of the type Cp'2LnR (Cp' = eta-5-Me5C5; Ln = La, Nd, Sm, Y, Lu; R = Nd; R = CH(SiMe3)2), Cp'2Sm, and Cp'2Sm(THF)2 catalyze the rapid dehydrogenative oligomerization of PhSiH3. Kinetic and mechanistic arguments exclude the importance of metal-centered redox processes in the catalytic cycle and support instead ''four-center'' ''heterolytic'' bond-scission/bond-forming sequences.
The Yersinia pestis Effector YopM Inhibits Pyrin Inflammasome Activation (2016)

Type III secretion systems (T3SS) are central virulence factors for many pathogenic Gram-negative bacteria, and secreted T3SS effectors can block key aspects of host cell signaling. To counter this, innate immune responses can also sense some T3SS components to initiate anti-bacterial mechanisms. The Yersinia pestis T3SS is particularly effective and sophisticated in manipulating the production of pro-inflammatory cytokines IL-1β and IL-18, which are typically processed into their mature forms by active caspase-1 following inflammasome formation. Some effectors, like Y. pestis YopM, may block inflammasome activation. Here we show that YopM prevents Y. pestis induced activation of the Pyrin inflammasome induced by the RhoA-inhibiting effector YopE, which is a GTPase activating protein. YopM blocks YopE-induced Pyrin-mediated caspase-1 dependent IL-1β/IL-18 production and cell death. We also detected YopM in a complex with Pyrin and kinases RSK1 and PKN1, putative negative regulators of Pyrin. In contrast to wild-type mice, Pyrin deficient mice were also highly susceptible to an attenuated Y. pestis strain lacking YopM, emphasizing the importance of inhibition of Pyrin in vivo. A complex interplay between the Y. pestis T3SS and IL-1β/IL-18 production is evident, involving at least four inflammasome pathways. The secreted effector YopJ triggers caspase-8- dependent IL-1β activation, even when YopM is present. Additionally, the presence of the T3SS needle/translocon activates NLRP3 and NLRC4-dependent IL-1β generation, which is blocked by YopK, but not by YopM. Taken together, the data suggest YopM specificity for obstructing the Pyrin pathway, as the effector does not appear to block Y. pestis-induced NLRP3, NLRC4 or caspase-8 dependent caspase-1 processing. Thus, we identify Y. pestis YopM as a microbial inhibitor of the Pyrin inflammasome. The fact that so many of the Y. pestis T3SS components are participating in regulation of IL-1β/IL-18 release suggests that these effects are essential for maximal control of innate immunity during plague.
Testing Bond Strength, a Review of the Literature (2009)

Objectives: Worldwide bond strength tests are used to evaluate bonding effectiveness of different adhesive techniques. The purpose of this study was to systematically collect these data to identify the primary parameters that affect the outcome of bond strength tests, and to attempt to disclose trends in adhesive performance of the different adhesive approaches today available. Materials and Methods: 871 studies were identified by entering the search term ‘dentin bond strength AND "published last 5 years"[Filter]’ in PubMed, and subsequently inserted in a custom-made database. Only studies containing data on the adhesion of several commercial adhesives to dentin were retained. Besides the actual bond strength data (mean, SD, n and number of pre-testing failures), other relevant parameters were recorded with regard to the substrate bonded to, surface preparation, storage conditions, potential artificial ageing, alternative application techniques, type of composite used, and some specific test conditions. Results: Up to now, 328 studies have been evaluated and from 110 studies relevant data were extracted, yielding 961 individual bond strength tests. A relatively simple statistical general linear model was generated to identify relevant parameters. The bond strength test used most often was the micro-tensile bond strength test (µTBS: 67%), followed by the macro-shear (MSB: 18%), micro-shear (µSB: 9%), macro-tensile (MTB: 4%) and push-out bond strength test (PoB: 2%). For further analysis, the push-out bond strengths and the adhesives that had been tested in less than 3 studies were excluded. From the remaining data, 56% involved any kind of experimental parameter as artificial aging, altered application techniques, etc. The actual bond strength obtained was significantly affected by the type of test employed (on average 29.2 and 18.1 MPa for µTBS and MSB respectively, p<0.0001). Significant differences were also observed for the different adhesive classes (pooled data): three-step etch&rinse (mean ± 95% confidence interval: 36.9 ± 5.8, n=44;), two-step etch&rinse (26.3 ± 1.7, n=178), two-step self-etch (32.3 ± 2, n=163) and one-step self-etch adhesives (23.6 ± 1.4, n=253). Also between individual adhesives substantial differences were observed in the mean bond strengths, ranging from 49 MPa (OptiBond Fl, Kerr) to 10 MPa (Futurabond NR, Voco). About 36% of the groups involved any kind of artificial aging and this affected the outcome significantly (22.5 MPa versus 27 MPa for the control specimens, p<0.001). Another remarkable parameter was the flexural modulus of the composite used; a lower flexural modulus was significantly correlated with lower bond strengths. Conclusions: Although preliminary, this systematic analysis of the bond strength data in literature revealed some key parameters that affect the outcome of bond strength tests.
Balanced electron drift oxide etcher with Xe added gas chemistry for low cost and high performance contact metallization (1999)

A new plasma source called balanced electron drift (BED) magnetron plasma was developed for SiO/sub 2/ contact/via hole etching. E/spl times/B drift of electrons, which is notorious for degrading the uniformity of magnetron plasmas (Sekine et al, 1995), has been completely balanced by applying appropriate 100 MHz RF power to the upper ring electrode. As a result, highly uniform self bias voltage (/spl Delta/V/sub DC/<4 V) and ion flux (/spl Delta/J/sub ion/</spl plusmn/3%) profiles were obtained on a 200 mm wafer. The BED etcher has the additional benefit of reducing dopant deactivation in the Si substrate due to the reduction in carbon implantation. Also, the addition of Xe, with a large mass number of 131 and large atomic radius of 2.17 /spl Aring/, has been confirmed to exhibit drastic suppression of dopant deactivation, which results in low contact resistance without additional ion implantation after contact etch.
Data from EGF816 Exerts Anticancer Effects in Non–Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor (2023)

&lt;div&gt;Abstract&lt;p&gt;Non–small cell lung cancer patients carrying oncogenic EGFR mutations initially respond to EGFR-targeted therapy, but later elicit minimal response due to dose-limiting toxicities and acquired resistance. EGF816 is a novel, irreversible mutant-selective EGFR inhibitor that specifically targets EGFR-activating mutations arising &lt;i&gt;de novo&lt;/i&gt; and upon resistance acquisition, while sparing wild-type (WT) EGFR. EGF816 potently inhibited the most common EGFR mutations L858R, Ex19del, and T790M &lt;i&gt;in vitro&lt;/i&gt;, which translated into strong tumor regressions &lt;i&gt;in vivo&lt;/i&gt; in several patient-derived xenograft models. Notably, EGF816 also demonstrated antitumor activity in an exon 20 insertion mutant model. At levels above efficacious doses, EGF816 treatment led to minimal inhibition of WT EGFR and was well tolerated. In single-dose studies, EGF816 provided sustained inhibition of EGFR phosphorylation, consistent with its ability for irreversible binding. Furthermore, combined treatment with EGF816 and INC280, a cMET inhibitor, resulted in durable antitumor efficacy in a xenograft model that initially developed resistance to first-generation EGFR inhibitors via cMET activation. Thus, we report the first preclinical characterization of EGF816 and provide the groundwork for its current evaluation in phase I/II clinical trials in patients harboring EGFR mutations, including T790M. &lt;i&gt;Cancer Res; 76(6); 1591–602. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Molecular Engineering of a Two-Step Transcription Amplification (TSTA) System for Transgene Delivery in Prostate Cancer (2002)

Gene therapy is founded on the concept that tissue-specific promoters can express heterologous genes for molecular imaging or therapeutic applications. The engineering of cell-specific enhancers to improve potency and the development of two-step transcriptional activation (TSTA) approaches have significantly improved the efficacy of transgene expression. Here we combine these technologies to create a robust, titratable, androgen-responsive system targeted to prostate cancer cells. Our "chimeric" TSTA system uses a duplicated variant of the prostate-specific antigen (PSA) gene enhancer to express GAL4 derivatives fused to one, two, or four VP16 activation domains. We targeted the resulting activators to cells with reporter templates bearing one, two, or five GAL4 binding sites upstream of firefly luciferase. We monitored activity via firefly luciferase assays in transfected cell extracts and in live nude mice using a cooled charge-coupled device (CCD) imaging system. In this system, we found that firefly luciferase expression in prostate cancer cells can be varied over an 800-fold range. We also found that a single plasmid bearing the optimized enhancer, GAL4-VP16 derivative, and reporter expressed firefly luciferase at 20-fold higher levels than the cytomegalovirus enhancer. We discuss the implications of this strategy and its application to molecular imaging and therapy.
Effect of tensile deformation on variant selection in {225}γ plate martensite and {557}γ lath martensite (2019)

The effect of tensile deformation on variant selection has been studied in {225}γ plate martensite and {557}γ lath martensite formed in high- and low-carbon steels, respectively. Different thermomechanical treatments are performed to analyse the effect of applied tensile stress, in the elastic and plastic range and the effect of prior plastic tensile deformation on variant selection. The variant selection is studied by computing the work of the deformation associated with the transformation in the applied stress field. Our analysis indicates that the deformation that needs to be considered to model the selection is based on lattice strains combinations. For {225}γ plate martensite, the average deformation resulting from the combination of the lattice strains of twin-related variants is the relevant deformation gradient for the work computation. On the contrary, in lath martensite, the combination of the lattice strains of low-misoriented variants appears to better model the selection phenomenon.
The Throughput-Outage Tradeoff of Wireless One-Hop Caching Networks (2013)

We consider a wireless device-to-device (D2D) network where the nodes have pre-cached information from a library of available files. Nodes request files at random. If the requested file is not in the on-board cache, then it is downloaded from some neighboring node via one-hop "local" communication. An outage event occurs when a requested file is not found in the neighborhood of the requesting node, or if the network admission control policy decides not to serve the request. We characterize the optimal throughput-outage tradeoff in terms of tight scaling laws for various regimes of the system parameters, when both the number of nodes and the number of files in the library grow to infinity. Our analysis is based on Gupta and Kumar {\em protocol model} for the underlying D2D wireless network, widely used in the literature on capacity scaling laws of wireless networks without caching. Our results show that the combination of D2D spectrum reuse and caching at the user nodes yields a per-user throughput independent of the number of users, for any fixed outage probability in $(0,1)$. This implies that the D2D caching network is "scalable": even though the number of users increases, each user achieves constant throughput. This behavior is very different from the classical Gupta and Kumar result on ad-hoc wireless networks, for which the per-user throughput vanishes as the number of users increases. Furthermore, we show that the user throughput is directly proportional to the fraction of cached information over the whole file library size. Therefore, we can conclude that D2D caching networks can turn "memory" into "bandwidth" (i.e., doubling the on-board cache memory on the user devices yields a 100\% increase of the user throughout).