gebhart/patrepeval huggingface dataset:
Abstract 954: The landscape of kinase fusions in cancer (2015)

Abstract Human cancer genomes harbor a variety of alterations leading to the deregulation of key pathways in tumor cells. The genomic characterization of tumors has uncovered numerous genes recurrently mutated, deleted or amplified, but gene fusions have not been studied as extensively. Kinase fusions represent ideal targets for the development of cancer drugs because they often confer oncogenic dependency in hematopoietic and solid malignancies as demonstrated by the success of several kinase inhibitors. For example, imatinib induces remission in leukemia patients who are positive for BCR-ABL1 fusions, and crizotinib and ceritinib have produced significant clinical benefit in patients with lung adenocarcinomas and mesenchymal tumors harboring ALK fusions. We have developed heuristics for reliably detecting gene fusion events in RNA-seq data sets and apply them to nearly 9,000 samples from The Cancer Genome Atlas. Fusions between any two genes were identified based on the number of chimeric reads and split reads. Then a number of filtering criteria were applied to flag false positive and non-functional fusions, including the removal of kinase fusions observed in a panel of more than 3,500 normal samples from diverse origins. Finally, we reviewed all recurrent kinase fusions manually to identify putative oncogenic drivers with distinctive characteristics of functional kinase fusions. We thereby were able to recapitulate most known translocation events in solid tumors (i.e., ALK, BRAF, EGFR, FGFR1, 2 and 3, NTRK1, 2 and 3, PDGFRA, PRKCA, RAF1, RET, ROS1). Interestingly, we identified new tumor types harboring such fusions and discovered several novel fusion partners for these kinases. We also detected several low-frequency, pan-cancer kinase fusion events, for example in the neurotrophic tyrosine receptor kinases NTRK1, NTRK2 and NTRK3, that drive tumorigenesis in a small fraction of multiple cancers, regardless of tissue type. Using our computational pipeline, we identified several novel and recurrent kinase fusions involving the MET proto-oncogene and PIK3CA. These bona fide oncogenes have not been shown previously to be activated by fusion events. Our analysis also uncovered novel, recurrent fusions in kinases with no known tumorigenic genomic alterations (e.g., FGR and PKN1), potentially resulting in active and oncogenic fusion proteins that represent putative targets for drug discovery. These findings have immediate diagnostic and clinical implications and expand the therapeutic options for cancer patients, as approved or exploratory drugs exist for many of these kinases. Citation Format: Nicolas Stransky, Ethan Cerami, Stefanie Schalm, Joseph L. Kim, Klaus Hoeflich, Christoph Lengauer. The landscape of kinase fusions in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 954. doi:10.1158/1538-7445.AM2015-954
Magnetohydrodynamic levitation for high-performance flexible pumps (2022)

We use magnetohydrodynamic levitation as a means to create a soft, elastomeric, solenoid-driven pump (ESP). We present a theoretical framework and fabrication of a pump designed to address the unique challenges of soft robotics, maintaining pumping performance under deformation. Using a permanent magnet as a piston and ferrofluid as a liquid seal, we model and construct a deformable displacement pump. The magnet is driven back and forth along the length of a flexible core tube by a series of solenoids made of thin conductive wire. The magnet piston is kept concentric within the tube by Maxwell stresses within the ferrofluid and magnetohydrodynamic levitation, as viscous lift pressure is created due to its forward velocity. The centering of the magnet reduces shear stresses during pumping and improves efficiency. We provide a predictive model and capture the transient nonlinear dynamics of the magnet during operation, leading to a parametric performance curve characterizing the ESP, enabling goal-driven design. In our experimental validation, we report a shut-off pressure of 2 to 8 kPa and run-out flow rate of 50 to 320 mL⋅min<sup>-1</sup>, while subject to deformation of its own length scale, drawing a total of 0.17 W. This performance leads to the highest reported duty point (i.e., pressure and flow rate provided under load) for a pump that operates under deformation of its own length scale. We then integrate the pump into an elastomeric chassis and squeeze it through a tortuous pathway while providing continuous fluid pressure and flow rate; the vehicle then emerges at the other end and propels itself swimming.
EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells (2017)

Epstein-Barr virus (EBV) infection converts resting human B cells into permanently proliferating lymphoblastoid cell lines (LCLs). The Epstein-Barr virus nuclear antigen 2 (EBNA2) plays a key role in this process. It preferentially binds to B cell enhancers and establishes a specific viral and cellular gene expression program in LCLs. The cellular DNA binding factor CBF1/CSL serves as a sequence specific chromatin anchor for EBNA2. The ubiquitous expression of this highly conserved protein raises the question whether additional cellular factors might determine EBNA2 chromatin binding selectively in B cells. Here we used CBF1 deficient B cells to identify cellular genes up or downregulated by EBNA2 as well as CBF1 independent EBNA2 chromatin binding sites. Apparently, CBF1 independent EBNA2 target genes and chromatin binding sites can be identified but are less frequent than CBF1 dependent EBNA2 functions. CBF1 independent EBNA2 binding sites are highly enriched for EBF1 binding motifs. We show that EBNA2 binds to EBF1 via its N-terminal domain. CBF1 proficient and deficient B cells require EBF1 to bind to CBF1 independent binding sites. Our results identify EBF1 as a co-factor of EBNA2 which conveys B cell specificity to EBNA2.
Sensors: A Printable Optical Time‐Temperature Integrator Based on Shape Memory in a Chiral Nematic Polymer Network (Adv. Funct. Mater. 21/2013) (2013)

On page 2723, Albertus P. H. J. Schenning, Cees W. M. Bastiaansen, and co-workers report the fabrication of a printable, optical, irreversible temperature sensor (e.g., a time-temperature integrator) by mechanical embossing of a chiral nematic polymer network, which yields a green colored film. A permanent color shift to orange is observed at temperatures above the glass transition temperature of the embossed film. Cover design by ICMS Animation Studio TU/e.
Periostin forms a functional complex with IgA in human serum (2019)

Periostin is a novel member of the IgA-associated molecules. These results are of great potential use to understand the pathological roles of periostin in allergic diseases and, from a practical standpoint, to develop diagnostics or therapeutic agents against periostin.
Rapid Occurrence of Lymphoproliferative Disease After Pancreas-Kidney Transplantation Performed During Acute Primary Epstein-Barr Virus Infection (1997)

Generalized lymphoproliferative disease occurred in a 30-year-old woman 15 days after she underwent simultaneous pancreas-kidney transplantation. Because of the rapid progression of this disorder, it was necessary to remove the grafts and discontinue immunosuppression 19 days after transplantation. Serological analysis demonstrated that the patient, who was Epstein-Barr virus (EBV)-seronegative 3 months before, was seroconverting at the time of the transplantation. EBV therefore was acquired just before the transplantation, either by a blood transfusion 4 months earlier or from the patient's EBV-positive boyfriend. The latter source appeared most likely, as concluded from the investigation of the EBV strains from the patient's boyfriend and from the blood and organ donors. Donor origin of lymphoblastoid cells was excluded by sex chromosomal analysis. Initiation of immunosuppression during a primary EBV infection carries the risk of very rapid development of B-cell lymphoproliferative disease. This emphasizes the need for active monitoring of EBV infections in transplant recipients and for the development of preventive strategies.
Hydrostatic Pressure Shows That Lamellipodial Motility in Ascaris Sperm Requires Membrane-associated Major Sperm Protein Filament Nucleation and Elongation (1998)

Sperm from nematodes use a major sperm protein (MSP) cytoskeleton in place of an actin cytoskeleton to drive their ameboid locomotion. Motility is coupled to the assembly of MSP fibers near the leading edge of the pseudopod plasma membrane. This unique motility system has been reconstituted in vitro in cell-free extracts of sperm from Ascaris suum: inside-out vesicles derived from the plasma membrane trigger assembly of meshworks of MSP filaments, called fibers, that push the vesicle forward as they grow (Italiano, J.E., Jr., T.M. Roberts, M. Stewart, and C.A. Fontana. 1996. Cell. 84:105-114). We used changes in hydrostatic pressure within a microscope optical chamber to investigate the mechanism of assembly of the motile apparatus. The effects of pressure on the MSP cytoskeleton in vivo and in vitro were similar: pressures >50 atm slowed and >300 atm stopped fiber growth. We focused on the in vitro system to show that filament assembly occurs in the immediate vicinity of the vesicle. At 300 atm, fibers were stable, but vesicles often detached from the ends of fibers. When the pressure was dropped, normal fiber growth occurred from detached vesicles but the ends of fibers without vesicles did not grow. Below 300 atm, pressure modulates both the number of filaments assembled at the vesicle (proportional to fiber optical density and filament nucleation rate), and their rate of assembly (proportional to the rates of fiber growth and filament elongation). Thus, fiber growth is not simply because of the addition of subunits onto the ends of existing filaments, but rather is regulated by pressure-sensitive factors at or near the vesicle surface. Once a filament is incorporated into a fiber, its rates of addition and loss of subunits are very slow and disassembly occurs by pathways distinct from assembly. The effects of pressure on fiber assembly are sensitive to dilution of the extract but largely independent of MSP concentration, indicating that a cytosolic component other than MSP is required for vesicle-association filament nucleation and elongation. Based on these data we present a model for the mechanism of locomotion-associated MSP polymerization the principles of which may apply generally to the way cells assemble filaments locally to drive protrusion of the leading edge.
[Monoclonal antibodies (MIB 1, PC 10, 486p and p53) as prognostic factors for recurrent urothelial carcinoma of the urinary bladder]. (1993)

Using an immunohistochemical method expression of PCNA, Ki-67, 486p and p53 antigen was investigated in paraffin sections of 119 patients with primary transitional cell carcinoma of the bladder. The purpose of this study was to detect recurring G1 and G2 bladder tumours compared with non-recurrent tumours. A relative large fraction of labelled cells for PCNA and Ki-67 was found in recurring G1 and G2 carcinomas. Moreover, recurrent transitional cell carcinomas showed a more positive staining pattern for 486p and p53, in contrast to non-recurrent carcinomas. Immunohistochemistry of these four antigens seems to yield additional information about the possibility of recurrence in G1 and G2 bladder carcinomas, thus allowing early, i.e. more aggressive, therapy.
Computing and visualising intra‐voxel orientation‐specific relaxation–diffusion features in the human brain (2020)

Diffusion MRI techniques are used widely to study the characteristics of the human brain connectome in vivo. However, to resolve and characterise white matter (WM) fibres in heterogeneous MRI voxels remains a challenging problem typically approached with signal models that rely on prior information and constraints. We have recently introduced a 5D relaxation-diffusion correlation framework wherein multidimensional diffusion encoding strategies are used to acquire data at multiple echo-times to increase the amount of information encoded into the signal and ease the constraints needed for signal inversion. Nonparametric Monte Carlo inversion of the resulting datasets yields 5D relaxation-diffusion distributions where contributions from different sub-voxel tissue environments are separated with minimal assumptions on their microscopic properties. Here, we build on the 5D correlation approach to derive fibre-specific metrics that can be mapped throughout the imaged brain volume. Distribution components ascribed to fibrous tissues are resolved, and subsequently mapped to a dense mesh of overlapping orientation bins to define a smooth orientation distribution function (ODF). Moreover, relaxation and diffusion measures are correlated to each independent ODF coordinate, thereby allowing the estimation of orientation-specific relaxation rates and diffusivities. The proposed method is tested on a healthy volunteer, where the estimated ODFs were observed to capture major WM tracts, resolve fibre crossings, and, more importantly, inform on the relaxation and diffusion features along with distinct fibre bundles. If combined with fibre-tracking algorithms, the methodology presented in this work has potential for increasing the depth of characterisation of microstructural properties along individual WM pathways.
Supplementary Data from Composite Three-Marker Assay for Early Detection of Kidney Cancer (2023)

&lt;p&gt;PDF - 547KB, Supplementary Data.&lt;/p&gt;
Novel variation of the lipid A structure of serotype B lgt3 mutant Moraxella catarrhalis LOS (2012)

We suggest an adaptive control scheme for the control of in-phase and cluster synchronization in delay-coupled networks. Based on the speed-gradient method, our scheme adapts the topology of a network such that the target state is realized. It is robust towards different initial conditions as well as changes in the coupling parameters. The emerging topology is characterized by a delicate interplay of excitatory and inhibitory links leading to the stabilization of the desired cluster state. As a crucial parameter determining this interplay we identify the delay time. Furthermore, we show how to construct networks such that they exhibit not only a given cluster state but also with a given oscillation frequency. We apply our method to coupled Stuart-Landau oscillators, a paradigmatic normal form that naturally arises in an expansion of systems close to a Hopf bifurcation. The successful and robust control of this generic model opens up possible applications in a wide range of systems in physics, chemistry, technology, and life science.
From Annotated Genomes to Metabolic Flux Models and Kinetic Parameter Fitting (2003)

Significant advances in system-level modeling of cellular behavior can be achieved based on constraints derived from genomic information and on optimality hypotheses. For steady-state models of metabolic networks, mass conservation and reaction stoichiometry impose linear constraints on metabolic fluxes. Different objectives, such as maximization of growth rate or minimization of flux distance from a reference state, can be tested in different organisms and conditions. In particular, we have suggested that the metabolic properties of mutant bacterial strains are best described by an algorithm that performs a minimization of metabolic adjustment (MOMA) upon gene deletion. The increasing availability of many annotated genomes paves the way for a systematic application of these flux balance methods to a large variety of organisms. However, such a high throughput goal crucially depends on our capacity to build metabolic flux models in a fully automated fashion. Here we describe a pipeline for generating models from annotated genomes and discuss the current obstacles to full automation. In addition, we propose a framework for the integration of flux modeling results and high throughput proteomic data, which can potentially help in the inference of whole-cell kinetic parameters.
SOI Material Readiness for 45nm and Sub-45nm Device Options (2006)

IC scaling has accelerated. The official 3 year ITRS cycle between technology nodes is in reality 2 years. The 65nm technology node is moving into production and the next 45nm node is being defined. The industry has clearly moved into the nano scale integration era. What stands out in this race towards smaller dimensions is the central role that materials have occupied. Among the material innovations, engineered substrates with SOI as its more eminent example stand out. The advances being made by the industry in SOI manufacturing have matched the quality of prime Si epi bulk wafers. The further development of SOI towards atomic level quality control, the SOI engineering focusing on mobility enhancement, RF, smart power, automotive, optoelectronic or MEMS applications address both the miniaturization as well as the diversification requirements of the electronics industry. In summary, it will be discussed how substrate engineering is a key contributor that will help the IC industry keep on the higher density-more performance-less power scaling path.
PROPER DIFFUSION-WEIGHTED WINDOW LEVEL IN MR IMAGING IN ACUTE VIRAL ENCEPHALITIS AND HYPOXIC ISCHAEMIC ENCEPHALOPATHY (2016)

Introduction: Diffusion-weighted magnetic resonance (MR) imaging provides image contrast that is different from that provided by conventional MR techniques. Improper Paper Submission DateDiffusion weighted (DW) window level obscures the diffuse cortical abnormality on DW image, hence proper windowed Diffusion weighted images are must for evaluation of cortical and deep grey matter nuclei abnormality. The increased sensitivity of DWI sequences with regard to viral encephalitis/hypoxic ischaemic encephalopathy (HIE) has been shown in several studies This study was performed to evaluate the role of proper DWI window level (250/150) in the diagnosis of viral encephalitis and HIE vs improperly windowed (500-850/250-Paper Publication Date 400) DW images for evaluation of cortical and deep grey matter nuclei. Material and Methods: We performed conventional MRI including T1, T2-Weighted and DOI fluid attenuated inversion recovery (FLAIR) sequences and DWI in 16 patients with viral encephalitis and 02 patients of hypoxic ischaemic encephalopathy diagnosed on the basis of laboratory, clinical and radiologic findings. Gradient B value of diffusion was 0, 400 and 800. Properly windowed (250/150) DW image versus an improperly windowed (500-850/250-400) DW image were evaluated for evaluation of cortical and deep grey matter nuclei signal intensity. Results: Axial DW images were reviewed at a consistent window level of 250/150. DW image with proper window level of 250/150 shows that the cortical/ deep gray matter nuclei abnormality is more evident. Apparent diffusion coefficient (ADC) map further illustrates the cortical restricted diffusion. Although with improperly windowed DWI (500-850/250-400), there is accentuated greywhite matter differentiation, but improper window level obscures the diffuse cortical abnormality on DW image. With proper window level of DW images, diffusion restriction was picked up in all the 16 cases of acute viral encephalitis and 02 patients of HIE. Conclusion: Proper window level of DWI (250/150) is helpful in early diagnosis of acute viral encephalitis and hypoxic ischaemic encephalopathy.
Transplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity (2023)

Hemophilia A is the most common X-linked bleeding disorder affecting more than half-a-million individuals worldwide. Persons with severe hemophilia A have coagulation FVIII levels <1% and experience spontaneous debilitating and life-threatening bleeds. Advances in hemophilia A therapeutics have significantly improved health outcomes, but development of FVIII inhibitory antibodies and breakthrough bleeds during therapy significantly increase patient morbidity and mortality. Here we use sheep fetuses at the human equivalent of 16-18 gestational weeks, and we show that prenatal transplantation of human placental cells (10<sup>7</sup>-10<sup>8</sup>/kg) bioengineered to produce an optimized FVIII protein, results in considerable elevation in plasma FVIII levels that persists for >3 years post-treatment. Cells engraft in major organs, and none of the recipients mount immune responses to either the cells or the FVIII they produce. Thus, these studies attest to the feasibility, immunologic advantage, and safety of treating hemophilia A prior to birth.
Tricuspid and mitral valve regurgitation in a chronic canine model implanted with a novel leadless pacemaker (2021)

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Boston Scientific and Abbott Background One of the presumed advantages of leadless pacemaker (LP) therapy is that tricuspid regurgitation (TR) occurrence and severity would be less than with conventional pacemakers due to the absence of leads. However, TR and mitral regurgitation (MR) may also worsen due to chronic right ventricular (RV) pacing per se. Purpose To determine whether a novel LP is associated with increased TR and MR severity in a chronic canine model and to evaluate predictors of TR and MR worsening. Methods Healthy canine subjects were implanted with a novel LP programmed at a lower rate of 80/min. TR and MR were assessed by transthoracic echocardiography (TTE) prior to implant, at 90 days and at 18 months after implant. Further were assessed percentage of pacing, presence of pacing during TTE, and wall motion abnormalities (WMA) observed during TTE, indicating ventriculo-ventricular dyssynchronous pacing. Paired t-tests were performed to compare TR and MR severity before and after implant. Univariable and multivariable generalized estimating equation (GEE) models were used to evaluate factors predictive of increased TR and MR severity. Paired t-tests were used to evaluate whether the increase of TR and MR differed between subgroups where pacing or WMA were observed or not. Results An LP was implanted in 73 subjects. TR and MR severity at 90 days (n = 55) were significantly increased from baseline (p = 0.02 and 0.001, confidence intervals [CIs] 0.05-0.64 and 0.20-0.75, respectively); at 18 months (n = 37) TR severity remained significantly increased but MR did not (p = 0.01 and 0.62, CI [0.09, 0.69] and [-0.15, 0.25], respectively). Multivariable GEE (figure) showed that WMA and absence of TR at baseline are significant predictors for increased TR, while WMA and a shorter RV long axis are significant predictors for increased MR. Subgroup analysis demonstrated that TR and MR at day 90 were only significantly increased in subjects with observed pacing or WMA (n = 29; p = 0.0014 and p &amp;lt; 0.0001 respectively), but not in subjects without observed pacing or WMA (n = 26; p = 0.56 and 0.16, respectively). At 18 months, the same observation was found for TR but not MR (pacing or WMA [n = 15], p &amp;lt; 0.0001 and p = 0.33 respectively: no pacing or WMA [n = 26], p = 0.23 and 1, respectively). Conclusion In absence of pacing, the novel EMPOWER LP was not associated with increased TR and MR severity in a canine model. When pacing was observed TR and MR did increase. Increased MR severity did not persist at 18 months. Abstract Figure 1