gebhart/patrepeval huggingface dataset:
Abstract 2160: MEN1611, a novel α-selective PI3K inhibitor in solid tumors (2018)

Abstract The PI3K pathway regulates various cellular processes such as proliferation, growth, apoptosis and cytoskeletal rearrangement. This pathway is frequently de-regulated and considered an oncogenic driver in human cancer. In most solid tumors, the activation of the PI3K pathway is induced by mutations of the catalytic subunit PI3Kα, present in approximately 20% to 50% of breast cancer, 14% of colorectal cancer and in 5-10% of NSCLC. Besides being an actionable target, the PI3K pathway is implicated in de novo and acquired treatment resistant in various tumor types treated with targeted therapy. As a matter of fact, the most interesting antitumor activity with PI3K inhibitors has been observed in combination. Here, we present MEN1611 (previously PA799), a PI3-kinase inhibitor with a peculiar biochemical profile targeting with high inhibition potency the mutated forms of PI3Kα and PI3Kγ. In the current study we demonstrate the anticancer activity and the pharmacodynamic effects of MEN1611 as monotherapy or in combination with targeted therapies in both xenograft and PDX models of breast cancer and in colorectal cancer and in NSCLC models, all with defined genetic profiles. MEN1611, at a clinically relevant dose, showed good antitumor activity in combination with targeted therapy agents against breast cancer, colorectal cancer and NSCLC models bearing PI3Kα mutations. A reduced activity was instead observed when the tumor models were wild type for PI3Kα or had low levels of PTEN. The antitumor activity of MEN611 was supported by its pharmacodynamic activity. In all the models, both AKT and S6 phosphorylation, markers of PI3K inhibition, were significantly inhibited upon treatment. In agreement with the biochemical profile of the drug, in PTEN null xenograft models where the tumor driver is the PI3K β-isoform, we observed lower effects in term of antitumor activity and of molecular inhibition of the pathway. Last, MEN1611 induction of hyperglycemia and insulin release was studied in the tumor models at clinical relevant dose as a marker of class-effect toxicity. MEN1611 showed significant antitumor activity in combination with other targeted therapies in breast, colon and NSCL cancer PI3Kα mutant models. Our results support the evidence that MEN611 is a PI3Kα specific inhibitor and provided the basis for the planned phase IB/II. Citation Format: Giuseppe Merlino, Alessio Fiascarelli, Mario Bigioni, Alessandro Bressan, Clelia Irrissuto, Andrea Pellacani, Maurizio Scaltriti, Monica Binaschi. MEN1611, a novel α-selective PI3K inhibitor in solid tumors [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 2160.
Shell structure beyond the proton drip line studied via proton emission from deformed 141Ho (2008)

Fine structure in proton emission from the 7/2−[523] ground state and from the 1/2+[411] isomer in deformed nucleus 141Ho was studied by means of fusion-evaporation reactions and digital signal processing. Proton transitions to the first excited 2+ state in 140Dy, with the branching ratio of Ipgs(2+)=0.9±0.2% and Ipm(2+)=1.7±0.5%, were observed. The data are analyzed within the non-adiabatic weak coupling model assuming a large quadrupole deformation of the daughter nucleus 140Dy as predicted by the self-consistent theory. Implications of this result on coexistence effects around N=74 are discussed. Significant modifications of the proton shell structure when going from the valley of beta stability to the proton drip line are discussed in terms of self-consistent theory involving the two-body tensor interaction.
Integrated acoustically tunable optical filters: devices and applications (1991)

With the advent of ever more broadly tunable laser sources and filters, wavelength-division multiplexing has become a practical approach to high-capacity optical communication. The acousto-optic filter has a large tuning-range-to-channel-spacing ratio (250:1 nm), has low power consumption (10 mW per channel demonstrated to date1) and has been fabricated in a polarization-independent configuration (see Fig. 1).2
Epigenetic reprogramming by tumor-derived EZH2 gain-of-function mutations promotes aggressive 3D cell morphologies and enhances melanoma tumor growth (2015)

In addition to genetic alterations, cancer cells are characterized by myriad epigenetic changes. EZH2 is a histone methyltransferase that is over-expressed and mutated in cancer. The EZH2 gain-of-function (GOF) mutations first identified in lymphomas have recently been reported in melanoma (~2%) but remain uncharacterized. We expressed multiple EZH2 GOF mutations in the A375 metastatic skin melanoma cell line and observed both increased H3K27me3 and dramatic changes in 3D culture morphology. In these cells, prominent morphological changes were accompanied by a decrease in cell contractility and an increase in collective cell migration. At the molecular level, we observed significant alteration of the axonal guidance pathway, a pathway intricately involved in the regulation of cell shape and motility. Furthermore, the aggressive 3D morphology of EZH2 GOF-expressing melanoma cells (both endogenous and ectopic) was attenuated by EZH2 catalytic inhibition. Finally, A375 cells expressing exogenous EZH2 GOF mutants formed larger tumors than control cells in mouse xenograft studies. This study not only demonstrates the first functional characterization of EZH2 GOF mutants in non-hematopoietic cells, but also provides a rationale for EZH2 catalytic inhibition in melanoma.
Autonomously Tunable Filters for Interference Mitigation: Advances in Autonomously Switchable/Tunable RF/Microwave Filters for Interference Mitigation Without Operator Intervention (2020)

In wireless communication, there is a strong demand for tunable filters in scenarios that require adaptively coping with multiband interference in RF front ends. Tuning devices, ferroelectric capacitors, ferromagnetic-material-based devices, microelectromechanical systems capacitors, and piezoelectric-material-based devices are commonly used for center frequency tuning or bandwidth adjustment in tunable filter realizations. Tunable or switchable filters are essential for this desired adaptability. However, each type has thus far demonstrated its particular disadvantages. Typically, continuously tunable filters are difficult to design or require intensive use of resources to control accurately, while switchable filter banks have significant insertion loss from switching networks. Tuning capability in tunable filters often requires human intervention to control tuning frequencies or bandwidths. In this article, we introduce autonomously tunable filters to adaptively protect or mitigate receiver systems from unwanted or unreferenced signals in RF front ends using an RF-power-dependent coupling without extra control signals or closed-loop feedback of digital processing of the spectrum through analog-to-digital and digital-to-analog converters.
Hyaluronan and LYVE-1 and allograft function in lung transplantation recipients (2019)

Hyaluronan (HA) is associated with innate immune response activation and may be a marker of allograft dysfunction in lung transplant recipients. This was a prospective, single center study comparing levels of bronchioalveolar lavage (BAL) and serum HA and the HA immobilizer LYVE-1 in lung transplant recipients with and without acute cellular rejection (ACR). Chronic lung allograft dysfunction (CLAD)-free survival was also evaluated based on HA and LYVE-1 levels. 78 recipients were enrolled with a total of 115 diagnostic biopsies and 1.5 years of median follow-up. Serum HA was correlated with BAL HA (r = 0.25, p = 0.01) and with serum LYVE-1 (r = 0.32, p = 0.002). There was significant variation in HA and LYVE-1 over time, regardless of ACR status. Levels of serum HA (median 74.7 vs 82.7, p = 0.69), BAL HA (median 149.4 vs 134.5, p = 0.39), and LYVE-1 (mean 190.2 vs 183.8, p = 0.72) were not associated with ACR. CLAD-free survival was not different in recipients with any episode of elevated serum HA (HR = 1.5, 95% CI = 0.3-7.7, p = 0.61) or BAL HA (HR = 0.94, 95% CI = 0.2-3.6, p = 0.93). These results did not differ when stratified by bilateral transplant status. In this small cohort, serum HA, BAL HA, and LYVE-1 levels are not associated with ACR or CLAD-free survival in lung transplant recipients.
Front Matter: Volume 10537 (2018)

This PDF file contains the front matter associated with SPIE Proceedings Volume10537, including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.
Band-pass compressive sampling as an enabling technology for rapid wideband RF spectrum sensing (2016)

Spectrum is the lifeblood of the future wireless networks and the data storm driven by the emerging technologies like Internet of Things, video over wireless will lead to a pressing artificial spectrum scarcity. Future smart terminals will need to quickly assess the spectrum usage and opportunistically use the available spectrum to overcome this challenge. They require energy-efficient spectrum scanning capabilities. We developed quadrature analog-to-information converters (QAIC), an energy-efficient compressed-sampling (CS) hardware architecture to process band-pass signals especially at RF frequencies [1]. The band-pass CS QAIC system offers a novel approach to attack the search for the quick detection of interferers in a wideband spectrum in an energy-efficient way. We further demonstrated time segmentation and adaptive thresholding with a time-segmented QAIC (TS-QAIC) to extend the interferer detection capabilities without any additional silicon cost and area [2], [3]. Such detectors are key cornerstones for future multi-tiered shared spectrum access solutions with dynamic spectrum sensing.
Seeking criteria for biodiversity roofs under Finnish conditions (2017)

Urbanisation has caused many environmental problems, such as air pollution and the loss of biodiversity. One way to mitigate these problems is to expand green spaces. Roofs, as the last frontier, could be made full use of. Green roofs have become a hot topic in recent years. In this study, I investigated the ability of green roofs to support urban biodiversity by conducting a literature review, and then I sought the criteria for biodiversity roofs under Finnish conditions by interviewing ecologists. \n\nMy research questions in this study were 1) What kinds of habitats could be 'ideal ecosystems' to be mimicked on biodiversity roofs in Finland; 2) which plant species could exist on roofs and whether they contribute to biodiversity; 3) what kinds of substrates support the biodiversity on roofs; 4) whether green roofs support faunal diversity and what faunal taxa could exist on roofs; 5) if and how roof structural characteristics influence roof biodiversity; 6) what kinds of management are practiced on biodiversity roofs; 7) what are people s attitudes towards or perceptions of biodiversity roofs in general. \n\nIn this study, I conduct that 1) Sunny dry habitats, such as meadows and tundra, can be regarded as 'model ecosystems' for biodiversity roofs in the Finnish context. 2) Substrate heterogeneity is a key to biodiversity on green roofs. Different materials and different combinations of materials could be applied on the same roof to mimic diverse types of soil types in the most biodiverse Finnish ecosystems. 3) Native species from the model ecosystems are ideal plants for biodiversity roofs. Combining multiple greening methods on the same roof can be a solution to achieve 'instant greening effects' with only native species. 4) An ideal biodiversity roof in the Finnish context could support birds, bats, and invertebrates, such as spiders. To attract and support fauna, a roof needs a diverse plant community, as well as extra elements, such as deadwood. 5) Roof structural characteristics (i.e. roof height, size, slope, direction, location, and age) impact biodiversity by determining the accessibility to and the dispersal of flora and fauna, as well as microclimates on roofs. 6) Management, such as irrigation, might help biodiversity at least for newly established biodiversity roofs, but biodiversity roofs aim at being self-sustaining eventually. 7) People have generally positive attitudes towards green roofs, but their willingness to actually install a biodiversity roof is influenced by other issues, such as the financial cost and roof safety.
Division of Labor with a Workforce of One: Challenges in Specifying Effector and Memory T Cell Fate (2007)

In the course of the immune response against microbes, naïve T cells proliferate and generate varied classes of effector cells, as well as memory cells with distinct properties and functions. Owing to recent technological advances, some of the most imposing questions regarding effector and memory T cell differentiation are now becoming experimentally soluble: How many classes of antigen-specific T cells exist, and how malleable are they in their fate and in their functional state? How might a spectrum of cell fates be imparted to the clonal descendants of a single lymphocyte? Where, when, and how does pathogen-associated information refine the instruction, selection, and direction of newly activated T cells as they perform their tasks in different locations and times? Some surprising new glimpses ahead on these subjects and other yet-unanswered questions are discussed.
Regulation of the multiple promoters of the human aldolase A gene: response of its two ubiquitous promoters to agents promoting cell proliferation (1991)

The human aldolase A gene is transcribed from three distinct promoters, the two ubiquitous promoters PN and PH and the muscle specific promoter PM. In the present study, we investigate further aldolase A mRNA structure and expression. We demonstrate that the upstream N-type exon is, in fact, extremely heterogeneous. RNAse H mapping experiments permit quantification of relative abundance of N, M, and H type mRNAs and show that the level of transcripts containing the downstream H-type exon is at least 30 times higher than that of those containing N exon, in all tissues tested. Aldolase A level is up-regulated in proliferating cells. Here we show that both N and H type mRNAs, although barely detectable in normal liver, are highly expressed in human hepatomas biopsies. Furthermore, in human lymphocytes, N-type mRNA level is enhanced by serum treatment, while in cultured Hep G2 cells, both N-type and H-type mRNA levels are increased by serum and by the tumor promoting agent PMA. Using CAT constructs in transfection experiments, we demonstrate that the H exon plus its upstream region can function autonomously: the 420 base pairs upstream of the H exon are sufficient to confer to promoter PH an efficiency comparable that of the complete SV40 early promoter and enhancer in two cell lines.
Extending power-handling of high-power metamaterial phase-shifters using three-dimensional counter-rotated end-loaded dipoles (2017)

Through the careful consideration of field enhancement observed in individual unit cells, metamaterials can be designed for use in high power microwave (HPM) applications. However, power handling considerations are only one aspect of any metamaterial design's performance. Presented here are two metamaterial unit cell geometries which feature reconfigurable reflection phase behaviors intended for HPM reflectarray applications. The unit cells are comprised of two end-loaded dipoles (ELD) which are counter-rotated to eliminate cross-pol while achieving the desired reflection phase angle. It is shown that by extending a planar ELD to a volumetric (i.e., three-dimensional) design, the observed field enhancement can be drastically reduced thus providing a path for improved power-handling performance.
Reconstitution of a Defunct Glycolytic Pathway via Recruitment of Ambiguous Sugar Kinases (2005)

During a recent investigation of the persistence of substrate ambiguity in contemporary enzymes, we identified three distinct ambiguous sugar kinases embedded within the modern Escherichia coli genome [Miller, B. G., and Raines, R. T. (2004) Biochemistry 43, 6387-6392]. These catalysts are the YajF, YcfX, and NanK polypeptides, all of which possess rudimentary glucokinase activities. Here, we report on the discovery of a fourth bacterial kinase with ambiguous substrate specificity. AlsK phosphorylates the glucose epimer, d-allose, with a k(cat)/K(m) value of 6.5 x 10(4) M(-)(1) s(-)(1). AlsK also phosphorylates d-glucose, with a k(cat)/K(m) value that is 10(5)-fold lower than the k(cat)/K(m) value displayed by native E. coli glucokinase. Overexpression of the alsK gene relieves the auxotrophy of a glucokinase-deficient bacterium, demonstrating that weak enzymatic activities derived from ambiguous catalysts can provide organisms with elaborated metabolic capacities. To explore how ambiguous catalysts are recruited to provide new functions, we placed the glucokinase-deficient bacterium under selection for growth at the expense of glucose. Under these conditions, the bacterium acquires a spontaneous mutation in the putative promoter region of the yajF gene, a locus previously shown to encode a sugar kinase with relaxed substrate specificity. The point mutation regenerates a consensus sigma(70) promoter sequence that leads to a 94-fold increase in the level of yajF expression. This increase provides sufficient glucokinase activity for reconstitution of the defunct glycolytic pathway of the bacterial auxotroph. Our current findings indicate that ambiguous enzymatic activities continue to play an important role in the evolution of new metabolic pathways, and provide insight into the molecular mechanisms that facilitate the recruitment of such catalysts during periods of natural selection.
ADVANCED WCDMA RADIO NETWORK SIMULATOR (1999)

If only good coverage is required in GSM networks, high frequency reuse factors can be used. In that case the network capacity is directly determined by the number of available time slots, and no advanced radio control algorithms are needed. If high capacity is required and fractional loading is used in GSM networks, advanced radio resource management algorithms are required. Sophisticated network simulators are needed for algorithm development in GSM base station systems. Also, finding out the capacity for accurate network planning is difficult without radio network simulators. In UMTS the need for an advanced radio network simulator will further increase because of new services, higher bit rates, multiplexing of services, and because of the possible asymmetric capacity requirement between uplink and downlink. Additionally, the UTRA WCDMA air interface is more dynamic than the GSM air interface, and therefore, optimised radio resource management algorithms need to be developed to fully exploit the WCDMA capabilities. The algorithm development for highly loaded dynamic networks is not possible without accurate modelling in computer simulations. In this paper the modelling principles of a WCDMA radio network simulator are presented.
Physical Property Comparisons of Infrared Optical Materials (2017)

This chapter includes data on a large number of optical materials. The data were assembled by searching available sources such as existing handbooks and other compilations and also the scientific and technical literature into 1990. Data are collated and presented in formats intended to be readily useful to the reader, who is presumed to be an engineer, designer, or other applied scientist. Thus, lengthy discussions, even of the possible accuracy of the data, are largely avoided. It is hoped that the reader/user will be able to extract the needed information rapidly from the tables and graphs.
Subordinate Effect of -21M HLA-B Dimorphism on NK Cell Repertoire Diversity and Function in HIV-1 Infected Individuals of African Origin (2020)

Natural Killer (NK) cells play an important role in antiviral defense and their potent effector function identifies them as key candidates for immunotherapeutic interventions in chronic viral infections. Their remarkable functional agility is achieved by virtue of a wide array of germline-encoded inhibitory and activating receptors ensuring a self-tolerant and tunable repertoire. NK cell diversity is generated by a combination of factors including genetic determinants and infections/environmental factors, which together shape the NK cell pool and functional potential. Recently a genetic polymorphism at position -21 of HLA-B, which influences the supply of HLA-E binding peptides and availability of HLA-E for recognition by the inhibitory NK cell receptor NKG2A, was shown to have a marked influence on NK cell functionality in healthy human cytomegalovirus (HCMV) seronegative Caucasian individuals. In this study, -21 methionine (M)-expressing alleles supplying HLA-E binding peptides were largely poor ligands for inhibitory killer immunoglobulin-like receptors (KIRs), and a bias to NKG2A-mediated education of functionally-potent NK cells was observed. Here, we investigated the effect of this polymorphism on the phenotype and functional capacity of peripheral blood NK cells in a cohort of 36 African individuals with human immunodeficiency virus type 1 (HIV-1)/HCMV co-infection. A similarly profound influence of dimorphism at position -21 of HLA-B on NK cells was not evident in these subjects. They predominantly expressed African specific HLA-B and -C alleles that contribute a distinct supply of NKG2A and KIR ligands, and these genetic differences were compounded by the marked effect of HIV-1/HCMV co-infection on NK cell differentiation. Together, these factors resulted in a lack of correlation of the HLA-B -21 polymorphism with surface abundance of HLA-E and loss of the NK cell functional advantage in subjects with -21M HLA-B alleles. Instead, our data suggest that during HIV/HCMV co-infection exposure of NK cells to an environment that displays altered HLA-E ligands drives adaptive NKG2C+ NK cell expansions influencing effector responses. Increased efforts to understand how NK cells are functionally calibrated to self-HLA during chronic viral infections will pave the way to developing targeted therapeutic interventions to overcome the current barriers to enhancing immune-based antiviral control.
Low dose time-resolved CT-angiography in pediatric patients with venous malformations using 3rd generation dual-source CT: Initial experience (2016)

4D-CTA at 70 kVp is a fast imaging modality that provides comprehensive diagnostic information of venous malformations in pediatric patients and is very valuable for therapy planning. Radiation dose of 4D-CTA must be weighted against the diagnostic information as well as the potential risk for sedation and contrast administration during MRI.