gebhart/patrepeval huggingface dataset:
ISB 1342: A first-in-class CD38 T cell engager for the treatment of relapsed refractory multiple myeloma. (2021)

8044 Background: ISB 1342 is a bispecific antibody heterodimer based on the Ichnos proprietary Bispecific Engagement by Antibodies based on T cell receptor (BEAT) platform. ISB 1342 is a first-in-class CD38 T cell engager under investigation in subjects with relapsed multiple myeloma refractory to proteasome inhibitors (PIs), immunomodulators (IMiDs) and daratumumab (study ISB 1342-101). Methods: ISB 1342 was engineered with a single chain variable fragment (scFv) arm that specifically recognizes a cluster of differentiation (CD)3-epsilon (CD3ε) and a fragment antigen binding (Fab) arm which specifically recognizes CD38 and does not compete with daratumumab. By co-engaging CD3ε on T cells and CD38 on tumor cells, ISB 1342 redirects T cells to kill CD38-expressing tumor cells. This mechanism of action is differentiated from existing monospecific CD38 targeting therapies and was designed to overcome resistance to daratumumab in multiple myeloma. Results: In vitro, ISB 1342 killed a large range of CD38-expressing tumor cell lines (EC50:12 to 90 pM) with 8 to 239-fold superior efficacy than daratumumab. ISB 1342 was also able to efficiently kill CD38 low-intermediate-expressing tumor cells that were poorly killed by daratumumab. ISB 1342 retained the potency to kill CD38 low-intermediate-expressing tumor cells when used in sequential or concomitant combination with daratumumab. In addition, the presence of soluble CD38 or glucocorticoid did not impact ISB 1342 killing potency. ISB 1342 was constructed with a double LALA mutation that dampens the binding to Fcγ receptors and C1q. Consistently, ISB 1342 showed only residual Fc-mediated effector functions and its mechanism of tumor cell killing critically relies on the engagement and the activation of T lymphocytes. ISB 1342 showed a favorable on target specificity profile in vitro and was unable to activate T cells in the absence of CD38 positive target cells. Further, ISB 1342-induced tumor cell killing was not associated with a detectable T cell fratricide in vitro. Finally, the potency of ISB 1342 was assessed in vivo in a therapeutic model of a subcutaneously established Daudi tumor co-xenografted with human PBMCs. In marked contrast to daratumumab, which induced only a partial tumor control, ISB 1342 induced complete tumor eradication when injected intravenously weekly at 0.5 mg/kg. As anticipated, the ISB 1342 control molecule (ISB 1342_13DU) made of an irrelevant CD38 binder failed to control tumor growth. The release of the Granzyme A and B, TNF-alpha and CXCL-10 in the tumor micro-environment one week post-treatment was strongly and significantly increased by ISB 1342 but not by daratumumab and ISB 1342_13DU; this represents a correlate of anti-tumor immunity associated with ISB 1342 efficacy in vivo. Conclusions: Hence the higher potency of ISB 1342 relative to daratumumab supports the ongoing clinical development in multiple myeloma patients.
Protection coordination in active distribution grids with IEC 61850 (2012)

This paper presents an adaptive protection scheme developed for distribution networks that include large number of Distributed Energy Resources and are capable to dynamically change configuration, i.e. active in nature. The system is based on a centralized controller running the real-time analysis of the data received from the field Intelligent Electronic Devices and communicating with IEDs by means of IEC 61850 communications.
Improved Deconvolution of Protein Targets for Bioactive Compounds Using a Palladium Cleavable Chloroalkane Capture Tag (2016)

The benefits provided by phenotypic screening of compound libraries are often countered by difficulties in identifying the underlying cellular targets. We recently described a new approach utilizing a chloroalkane capture tag, which can be chemically attached to bioactive compounds to facilitate the isolation of their respective targets for subsequent identification by mass spectrometry. The tag minimally affects compound potency and membrane permeability, enabling target engagement inside cells. Effective enrichment of these targets is achieved through selectivity in both their rapid capture onto immobilized HaloTag and their subsequent release by competitive elution. Here, we describe a significant improvement to this method where selective elution was achieved through palladium-catalyzed cleavage of an allyl-carbamate linkage incorporated into the chloroalkane capture tag. Selective tag cleavage provided robust release of captured targets exhibiting different modes of binding to the bioactive compound, including prolonged residence time and covalent interactions. Using the kinase inhibitors ibrutinib and BIRB796 as model compounds, we demonstrated the capability of this new method to identify both expected targets and "off-targets" exhibiting a range of binding affinities, cellular abundances, and binding characteristics.
Innervation: the missing link for biofabricated tissues and organs (2020)

Innervation plays a pivotal role as a driver of tissue and organ development as well as a means for their functional control and modulation. Therefore, innervation should be carefully considered throughout the process of biofabrication of engineered tissues and organs. Unfortunately, innervation has generally been overlooked in most non-neural tissue engineering applications, in part due to the intrinsic complexity of building organs containing heterogeneous native cell types and structures. To achieve proper innervation of engineered tissues and organs, specific host axon populations typically need to be precisely driven to appropriate location(s) within the construct, often over long distances. As such, neural tissue engineering and/or axon guidance strategies should be a necessary adjunct to most organogenesis endeavors across multiple tissue and organ systems. To address this challenge, our team is actively building axon-based "living scaffolds" that may physically wire in during organ development in bioreactors and/or serve as a substrate to effectively drive targeted long-distance growth and integration of host axons after implantation. This article reviews the neuroanatomy and the role of innervation in the functional regulation of cardiac, skeletal, and smooth muscle tissue and highlights potential strategies to promote innervation of biofabricated engineered muscles, as well as the use of "living scaffolds" in this endeavor for both in vitro and in vivo applications. We assert that innervation should be included as a necessary component for tissue and organ biofabrication, and that strategies to orchestrate host axonal integration are advantageous to ensure proper function, tolerance, assimilation, and bio-regulation with the recipient post-implant.
Pre-diabetes is Associated with Attenuation rather than Volume of Epicardial Adipose Tissue on Computed Tomography (2022)

Abstract Background The volume of epicardial adipose tissue (EATV) is increased in type-2 diabetes (T2D), while its attenuation (EATA) appears to be decreased. Similar patterns have been suggested in pre-diabetes, but data is scarce. In both pre-diabetes and T2D, any independent role of EATV and EATA in disease development remains to be proven, a task complicated by their substantial co-variation with other anthropometrics (e.g. BMI, waist circumference, and abdominal visceral adipose tissue (VAT). Method EATV and EATA was quantified in computed tomography (CT) images in a population study (n = 1,948) using an automatic technique. Data was available on BMI, waist circumference, abdominal visceral adipose tissue (VAT) area, insulin resistance (IR) and glucose tolerance, the latter ranging from normal (NGT), over pre-diabetes (impaired fasting glucose [IFG, n = 414] impaired glucose tolerance [IGT, n = 321] and their combination [CGI, n = 128]), to T2D. Results EATV was increased in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI, however not when adjusting for waist or VAT. EATA was reduced in prediabetes, T2D and IR in univariable analyses and when adjusting for BMI and waist, however not when adjusting for VAT. Adjustment for other co-variates had little influence on the results. Conclusion EATV is increased and EATA reduced in pre-diabetes, T2D and IR, however, significant co-variation with other anthropometrics, especially VAT, obscures their function in disease development. The current results do not exclude a pathophysiological role of epicardial fat, but future studies need to adjust for anthropometrics, or focus on the microenvironment within the pericardial sac.
Self-Amorphizing Gas Cluster Ion Beam Technology and Combination with Laser Spike Anneal for Highly Scaled Source Drain Junction (2006)

High energy borane (B <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sub> ) gas cluster ion beam (GCIB) successfully enables a sub-10 nm box-shaped dopant profile without channeling tail, and steep gradient (2.5 nm/dec) in lateral direction. pFET using GCIB source/drain extension shows superior suppression of short channel effects and reduces the dependency of drive current on gate overlap capacitance variation for scaled devices. Moreover, the perimeter leakage component in p+/n-well junction was reduced compared to the conventional co-implantation process with pre-amorphization, which might come from novel self-amorphization mechanism by energized clusters without foreign impurities such as Ge and F. For further scaled devices, GCIB can provide more efficient boron activation by laser spike annealing (LSA) while maintaining the scaled extension profile by combination with the reduced temperature spike RTA
SINTERING OF PrCo5 PERMANENT MAGNETS (1971)

Permanent magnets were produced by liquid-phase sintering from PrCo5 with a Sm–Co and a Pr–Co alloy as sintering aids. The best values of the energy product achieved with these two additives are 21.1 and 16.6 MG Oe; the highest intrinsic coercive forces of different samples are 14 000 and 9470 Oe, respectively.
Spatial distribution of lasing at the edge of a photonic stop band in dye-doped cholesteric liquid crystals (2000)

We find a ring structure in the far field of laser radiation emitted from a dye-doped cholesteric liquid crystal (CLC) film. This is a consequence of angular confinement of radiation at the frequency of the mode propagating normal to the molecular layers, which lies closest to the reflection band edge. This is a result of the increase in frequency of the band edge with increasing angle from the normal, which places oblique radiation at the frequency of the band edge for normally propagating radiation inside the photonic gap. As a result, the intensity along the output surface of the film decays exponentially on a length scale that can be much larger than the film thickness. This in turn gives rise to a ring structure in the far field that is similar to Fraunhofer diffraction of a plane wave by an aperture. These results apply not only to CLC films but also to binary layered media.
FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer (2016)

Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor α (ER)-chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown. Here, we report preclinical evidence for a role of FOXA1 in Endo-R breast cancer as well as evidence for its clinical significance. FOXA1 is gene-amplified and/or overexpressed in Endo-R derivatives of several breast cancer cell line models. Induced FOXA1 triggers oncogenic gene signatures and proteomic profiles highly associated with endocrine resistance. Integrated omics data reveal IL8 as one of the most perturbed genes regulated by FOXA1 and ER transcriptional reprogramming in Endo-R cells. IL-8 knockdown inhibits tamoxifen-resistant cell growth and invasion and partially attenuates the effect of overexpressed FOXA1. Our study highlights a role of FOXA1 via IL-8 signaling as a potential therapeutic target in FOXA1-overexpressing ER-positive tumors.
Vergleich von PillCam-Kolonkapsel-Endoskopie mit der Koloskopie bei der Diagnostik kolorektaler Tumoren: Eine prospektive Pilotstudie (2007)

Background and aims: Colonoscopy is regarded as the gold standard for colorectal cancer (CRC) screening. PillCam capsule endoscopy could be an alternative approach for screening large populations. We report a pilot evaluation in humans of the safety, feasibility, and performance of colon capsule endoscopy compared with colonoscopy. Patients and methods: Patients included in this single-center comparative study had presented for screening colonoscopy or there was suspicion of polyps or CRC. The capsule was ingested in the morning. After excretion, colonoscopy was performed. Significant findings were defined either als polyps <6mm, or three or more polyps of any size. Colonoscopy and colon capsule endoscopy (CCE) review were performed by independent physicians. Results: 41 patients (26 women), mean age 56 years (range 26-75) were included, and all had complete colonoscopies. Four patients were excluded due to technical problems and one could not swallow the capsule; thus, 36 patients were considered in the analysis. In six the capsule had not been expelled at 10 hours and was retrieved endoscopically. CCE identified 19 of the 25 patients (76%) with positive findings and 10 of the 13 (77 %) with significant lesions detected by colonoscopy. CCE detected seven lesions not seen at colonoscopy and two tumors were detected by both examinations. Overall sensitivity of CCE to detect significant lesions was 77 %, specificity was 70 %, positive predictive value was 59%, and negative predictive value was 84%. No adverse events occurred. Conclusion: CCE showed promising accuracy compared with colonoscopy. This new noninvasive technique deserves further evaluation as a potential CRC screening tool. © 2007, Georg Thieme Verlag Stuttgart. All rights reserved.
Modular wireless inertial trackers for biomedical applications (2013)

In the past few years, semiconductor based wireless positing and tracking devices have successfully integrated into consumer electronics devices. The sensors track the movement and the orientation of the device to provide a positioning feedback to the program. However, the accuracy of these trackers is typically not acceptable for biomedical application which demands high accuracy. Previous study was performed to access the feasibility of using semiconductor based inertial measurement units (IMU) for human motion tracking. After evaluating the strength and weakness in the previous IMU modules, several modifications and improvement were made. A modular IMU was designed with high resolution ADC. A statistical based approach for orientation tracking is currently being developed and preliminary data were presented and compared with other tracking algorithms.
Web search (2007)

In scarcely a decade, web search has gone from simply scaling traditional information retrieval, to a groundswell of new opportunities that are changing marketing as we know it. In this lecture, we begin by reviewing the progress, pointing out that web search is no longer a purely computer sceince problem. We then hint at the role of other disciplines in this ongoing revolution and a number of directions for research.
A Micromachined Titanium Sputter Ion Pump for Cavity Pressure Control (2006)

This paper describes a micro-scale sputter ion pump and its use in the controlled reduction of pressure in a large cavity package. The pump is composed of titanium electrodes on a glass substrate which are sputtered away and form the source of Ti ions that react and bind with oxygen and nitrogen. The discharges are powered by DC and pulsed DC high voltage. The duration of applied voltage determines the amount of sputtered titanium and consequently, the pressure reduction inside a cavity. To date, the pressure inside sealed commercial packages of volumes 6.33 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> and 2.2 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> , has been reduced by 168 Torr and 126 Torr, respectively.
Needs, trends, and advances in scintillators for radiographic imaging and tomography (2022)

Scintillators are important materials for radiographic imaging and tomography (RadIT), when ionizing radiations are used to reveal internal structures of materials. Since its invention by Röntgen, RadIT now come in many modalities such as absorption-based X-ray radiography, phase contrast X-ray imaging, coherent X-ray diffractive imaging, high-energy X- and $γ-$ray radiography at above 1 MeV, X-ray computed tomography (CT), proton imaging and tomography (IT), neutron IT, positron emission tomography (PET), high-energy electron radiography, muon tomography, etc. Spatial, temporal resolution, sensitivity, and radiation hardness, among others, are common metrics for RadIT performance, which are enabled by, in addition to scintillators, advances in high-luminosity accelerators and high-power lasers, photodetectors especially CMOS pixelated sensor arrays, and lately data science. Medical imaging, nondestructive testing, nuclear safety and safeguards are traditional RadIT applications. Examples of growing or emerging applications include space, additive manufacturing, machine vision, and virtual reality or `metaverse'. Scintillator metrics such as light yield and decay time are correlated to RadIT metrics. More than 160 kinds of scintillators and applications are presented during the SCINT22 conference. New trends include inorganic and organic scintillator heterostructures, liquid phase synthesis of perovskites and $μ$m-thick films, use of multiphysics models and data science to guide scintillator development, structural innovations such as photonic crystals, nanoscintillators enhanced by the Purcell effect, novel scintillator fibers, and multilayer configurations. Opportunities exist through optimization of RadIT with reduced radiation dose, data-driven measurements, photon/particle counting and tracking methods supplementing time-integrated measurements, and multimodal RadIT.
Targeting the APP-Mint2 Protein–Protein Interaction with a Peptide-Based Inhibitor Reduces Amyloid-β Formation (2021)

There is an urgent need for novel therapeutic approaches to treat Alzheimer's disease (AD) with the ability to both alleviate the clinical symptoms and halt the progression of the disease. AD is characterized by the accumulation of amyloid-β (Aβ) peptides which are generated through the sequential proteolytic cleavage of the amyloid precursor protein (APP). Previous studies reported that Mint2, a neuronal adaptor protein binding both APP and the γ-secretase complex, affects APP processing and formation of pathogenic Aβ. However, there have been contradicting results concerning whether Mint2 has a facilitative or suppressive effect on Aβ generation. Herein, we deciphered the APP-Mint2 protein-protein interaction (PPI) via extensive probing of both backbone H-bond and side-chain interactions. We also developed a proteolytically stable, high-affinity peptide targeting the APP-Mint2 interaction. We found that both an APP binding-deficient Mint2 variant and a cell-permeable PPI inhibitor significantly reduced Aβ<sub>42</sub> levels in a neuronal <i>in vitro</i> model of AD. Together, these findings demonstrate a facilitative role of Mint2 in Aβ formation, and the combination of genetic and pharmacological approaches suggests that targeting Mint2 is a promising therapeutic strategy to reduce pathogenic Aβ levels.
Improving Mention Detection Robustness to Noisy Input (2010)

Information-extraction (IE) research typically focuses on clean-text inputs. However, an IE engine serving real applications yields many false alarms due to less-well-formed input. For example, IE in a multilingual broadcast processing system has to deal with inaccurate automatic transcription and translation. The resulting presence of non-target-language text in this case, and non-language material interspersed in data from other applications, raise the research problem of making IE robust to such noisy input text. We address one such IE task: entity-mention detection. We describe augmenting a statistical mention-detection system in order to reduce false alarms from spurious passages. The diverse nature of input noise leads us to pursue a multi-faceted approach to robustness. For our English-language system, at various miss rates we eliminate 97% of false alarms on inputs from other Latin-alphabet languages. In another experiment, representing scenarios in which genre-specific training is infeasible, we process real financial-transactions text containing mixed languages and data-set codes. On these data, because we do not train on data like it, we achieve a smaller but significant improvement. These gains come with virtually no loss in accuracy on clean English text.
Translucent photonic network dimensioning for equipment cost minimization (2004)

Network design method is proposed by combining advantages of link-based and path-based approaches. A trial design incorporating precise optical characteristics modeling showed 30% cost reduction while guaranteeing optical signal reachability for any possible traffic demands.
OpenRooms: An Open Framework for Photorealistic Indoor Scene Datasets (2021)

We propose a novel framework for creating large-scale photorealistic datasets of indoor scenes, with ground truth geometry, material, lighting and semantics. Our goal is to make the dataset creation process widely accessible, transforming scans into photorealistic datasets with high-quality ground truth for appearance, layout, semantic labels, high quality spatially-varying BRDF and complex lighting, including direct, indirect and visibility components. This enables important applications in inverse rendering, scene understanding and robotics. We show that deep networks trained on the proposed dataset achieve competitive performance for shape, material and lighting estimation on real images, enabling photorealistic augmented reality applications, such as object insertion and material editing. We also show our semantic labels may be used for segmentation and multi-task learning. Finally, we demonstrate that our framework may also be integrated with physics engines, to create virtual robotics environments with unique ground truth such as friction coefficients and correspondence to real scenes. The dataset and all the tools to create such datasets will be made publicly available. <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup>
External I/O interfaces in sub-5nm GAA NS Technology and STCO Scaling Options (2021)

In this paper, the challenges of the I/O development roadmap are discussed. The impact of I/O application in FEOL scaling and 3D integration are evaluated. A cost-efficient circuit solution to the I/O implementation in a gate-all-around (GAA) nanosheet (NS) technology is proposed. The functionality verification and the relevant reliability concerns are assessed in a mature industrial CMOS process. Finally, to foresee the design strategies in future STCO scaling era, the impact of the fully back-side (BS) connections on I/O performance is investigated. Capacitance is doubled compared to front-side (FS) I/O due to the contributions from BS connection layers. The layout techniques can mitigate ~30% of the extra capacitance and the technology option of the deep trench isolation (DTI) is considered to reduce the extra capacitance to only ~8%.