gebhart/patrepeval huggingface dataset:
2G12-Expressing B Cell Lines May Aid in HIV Carbohydrate Vaccine Design Strategies (2012)

The highly conserved cluster of high-mannose glycans on the HIV-1 envelope glycoprotein, gp120, has been highlighted as a target for neutralizing antibodies. 2G12, the first HIV-1 antiglycan neutralizing antibody described, binds with an unusual domain-exchanged structure that creates a high-affinity multivalent binding surface. It is an interesting challenge for rational vaccine design to generate immunogens capable of eliciting domain-exchanged 2G12-like responses. We recently showed that di-mannose recognition by the variable domains of 2G12 is independent of domain exchange but that exchange is critical for virus neutralization. Carbohydrate-based immunogens aimed at inducing 2G12-like antibodies may need to drive both di-mannose recognition and domain exchange through interactions with B cell receptors. Here we assessed the ability of such immunogens to activate mouse B cell lines displaying domain-exchanged wild-type 2G12 (2G12 WT), a non-domain-exchanged Y-shaped variant (2G12 I19R), and germ line 2G12 (2G12 gl). We show that several immunogens, including heat-killed yeast and bacteria, can activate both 2G12 WT and 2G12 I19R B cells. However, only discrete clusters of high-mannose glycans, as on recombinant forms of the HIV-1 envelope trimer and oligodendrons, activate 2G12 WT B cells. Furthermore, no immunogen tested activated 2G12 gl cells. Our results support the hypothesis that in order to drive domain exchange of an antimannose antibody response, a boost with an immunogen displaying discrete clusters of high-mannose glycans not recognized by conventional Y-shaped antibodies will be required. Additionally, a molecule capable of activating 2G12 gl cells might also be required. The results highlight broadly neutralizing antibody-expressing mouse B cells as potentially useful tools for carbohydrate immunogen screening.
A Framework for Manipulating Deformable Linear Objects by Coherent Point Drift (2018)

Manipulation of deformable linear objects is a challenging task for robots. These objects have infinite-dimensional configuration space and are computational-expensive to model, making it difficult for real-time tracking, planning and control. To deal with these challenges, a uniform framework that includes state estimation, task planning, and trajectory planning is proposed in this letter based on the concept of coherent point drift (CPD). A real-time observer is proposed to estimate the states of deformable objects from the perceived point clouds. An online task planner is then developed to recognize the manipulation step according to the state estimation result. For trajectory planning, human operators first train robots example trajectories given several object states. In the test stage, a new feasible trajectory can be autonomously generated by a smooth transformation from training scenarios to test scenarios. A series of rope manipulation experiments on a dual-arm robotic platform are performed to validate the effectiveness of the proposed methods.
AlN/AlGaN HEMTs on AlN substrate for stable high‐temperature operation (2014)

An AlN/AlGaN high‐electron‐mobility transistor (HEMT) fabricated on a free‐standing AlN substrate is demonstrated. A metal stack, composed of Zr/Al/Mo/Au, was found to show low contact resistivity for source and drain ohmic contacts. The fabricated AlN/AlGaN HEMT exhibited a maximum drain current of 38 mA/mm with a threshold voltage of −3.4 V. Negligible drain current degradation was observed at temperatures from 300 to 573 K, demonstrating that an AlN/AlGaN approach on an AlN substrate is promising for stable high‐temperature operation.
An In Vitro Model for Studying Growth and Effect of Trauma and External Agents on the Cricoid at the Cellular Level (1992)

Over the past several years it has become evident that expansion laryngotracheal surgery is effective in the treatment of laryngotracheal stenosis. Several clinical and animal studies have been performed to study the process of laryngotracheal stenosis and its treatment. However, there are still many questions that cannot be addressed by currently used clinical and animal research. Further indepth study of the behavior of the subglottis at the cellular level is necessary. We present an in vitro model for studying chondrocyte metabolism of the bovine cricoid. Cartilage was successfully grown in an explant culture system, and it was shown that the chondrocytes were metabolically active and responded to external agents. This model will serve to study the mechanism of growth and effects of trauma and external agents on the cricoid at the cellular level.
Aryl hydrocarbon receptor signaling plays a significant role in mediating benzo[a]pyrene- and cigarette smoke condensate-induced cytogenetic damage in vivo (2001)

This laboratory has previously reported data suggesting that aryl hydrocarbon receptor (AhR) signaling may have a net potentiating effect on the DNA damaging potential of cigarette smoke. The experiments described in this report extend these studies by testing whether the potent AhR antagonist 3'-methoxy-4'-nitroflavone (3'M4'NF) can modify the in vivo genetic toxicity of benzo[a]pyrene (B[a]P) and the complex mixture of chemicals in cigarette smoke condensate (CSC). Initial experiments were designed to determine 3'M4'NF doses which can antagonize AhR in vivo but which have little effect on constitutive cytochrome P4501A (CYP1A) activity. These experiments took three forms: (i) zoxazolamine paralysis tests, a functional assay of cytochrome P450 CYP1A activity in 3'M4'NF-treated C57Bl/6J mice; (ii) co-treatment of AHR: null allele mice with 150 mg/kg B[a]P plus a range of 3'M4'NF concentrations in order to evaluate the potential of the flavone to interact with non-AhR targets which may affect B[a]P toxicity; (iii) an evaluation of the in vivo AhR antagonist activity of 3'M4'NF using transgenic mice which carry a dioxin-responsive element-regulated lacZ reporter. Once an appropriate dose range was determined, C57Bl/6J mice were challenged with B[a]P or CSC with and without 3'M4'NF co-treatment. Chromosome damage was measured by scoring the frequency of micronuclei in peripheral blood reticulocytes. Data presented herein suggest that 3'M4'NF can protect mice from B[a]P-induced bone marrow cytotoxicity and genotoxicity. Furthermore, CSC-associated genotoxicity was abolished by the flavonoid. These data add support to our hypothesis that AhR signaling has a net potentiating effect on the genetic toxicity and, presumably, carcinogenicity of cigarette smoke.
Dielectric elastomers: past, present, and potential future (2018)

Dielectric elastomer (DE) technology is based on the interactions of electrostatic charge with deformable polymer materials. While such materials and their electrical interactions have a long history of investigation, the discovery in the early 1990s that certain thin elastomer films, such as silicone films, were capable of supporting significant electric stress and producing large mechanical output increased interest in this phenomenon. This paper discusses the history of DE technology, presents developments, and considers future progress. Discoveries of large strain outputs with commercially available polymer films has allowed many researchers world-wide to research the technology and explore a wide range of applications. As the technology has matured, new modalities of the fundamental DE operation have emerged. In addition to actuators, researchers began to develop sensors and generators based on the technology. Additionally, explorations of the component materials, actuator geometries, electrode materials, packaging for environmental factors and high-voltage electronics are addressing the lifetime and other limitations of the technology. Examples addressing lifetime include: bistable and shape-memory configurations and self-clearing, carbon nanotubes electrodes. Improved modeling and failure mode investigations are also enabling the technology to progress. A number of commercial products based on DE technology have already hit the market. Although the impact of DEs thus far is well below that of other transducer technologies such as electromagnetics, their technical story and potential continue to expand.
Liquid Oxygen / Liquid Methane Co-Axial Swirl Injector Development (2010)

The propellant combination of liquid methane and liquid oxygen has been the focus of many research and design programs in the past few years. This paper focuses on the investigation of an increase in performance of a liquid oxygen (LOX) / liquid methane (LCH4) engine through the use of a liquid/liquid co-axial swirl injector. This injection scheme is an unlike impinging type which uses concentric injection orifices that inject both propellants in the liquid phase and with a designed angular momentum. This creates a swirling cone of each propellant which will then impinge together. An experimental engine is described which has been developed with multiple injection elements of this type to generate 1805 N (406 lbf) of thrust. To investigate the performance of the injection elements, the engine is scheduled to be hot fire tested early this fall. The data collected will then be compared to a reference engine that has a configuration which is extremely similar except for the injection method. This will allow for the quantification of the change in performance of the engine caused by the injection method.
Automatic determination of the artery vein ratio in retinal images (2010)

A lower ratio between the width of the arteries and veins (Arteriolar-to-Venular diameter Ratio, AVR) on the retina, is well established to be predictive of stroke and other cardiovascular events in adults, as well as an increased risk of retinopathy of prematurity in premature infants. This work presents an automatic method that detects the location of the optic disc, determines the appropriate region of interest (ROI), classifies the vessels in the ROI into arteries and veins, measures their widths and calculates the AVR. After vessel segmentation and vessel width determination the optic disc is located and the system eliminates all vessels outside the AVR measurement ROI. The remaining vessels are thinned, vessel crossing and bifurcation points are removed leaving a set of vessel segments containing centerline pixels. Features are extracted from each centerline pixel that are used to assign them a soft label indicating the likelihood the pixel is part of a vein. As all centerline pixels in a connected segment should be the same type, the median soft label is assigned to each centerline pixel in the segment. Next artery vein pairs are matched using an iterative algorithm and the widths of the vessels is used to calculate the AVR. We train and test the algorithm using a set of 25 high resolution digital color fundus photographs a reference standard that indicates for the major vessels in the images whether they are an artery or a vein. We compared the AVR values produced by our system with those determined using a computer assisted method in 15 high resolution digital color fundus photographs and obtained a correlation coefficient of 0.881.
Identification of different gas-phase reaction modes of WF<sub>6</sub> with SiH<sub>4</sub> for deposition of WSi<i><sub>n</sub></i> films: powder formation and WSi<i><sub>n</sub></i> cluster synthesis (2018)

2018 International Conference on Solid State Devices and Materials,Identification of different gas-phase reaction modes of WF<sub>6</sub> with SiH<sub>4</sub> for deposition of WSi<i><sub>n</sub></i> films: powder formation and WSi<i><sub>n</sub></i> cluster synthesis
Design of Freeform Illumination Optics (2018)

Abstract Freeform optics constitutes a new technology that is currently driving substantial changes in illumination design. It liberates designers and engineers from restrictions of optical surface geometry, enabling them to achieve compact, lightweight, and efficient illumination systems with excellent optical performance. Freeform optics is currently used widely for both fundamental research and practical applications. This Review focuses on the design of freeform illumination optics, which is a key factor in advancing the development of illumination engineering. The design methods of freeform illumination optics can be divided into two groups: zero‐étendue algorithms based on ideal source assumption and design algorithms for extended light sources. The zero‐étendue algorithms include ray mapping method, Monge–Ampère equation method, and supporting quadric method. The algorithms for extended sources include illumination optimization, feedback design, and simultaneous multiple surfaces method. The characteristics and limitations of these design methods are illustrated and a summary of these methods with future outlooks is also given.
An Enolisable Barbiturate with Adjustable Hydrogen‐Bonding Structure for UV/Vis Detection of Nucleic Acid Bases and Related Compounds (2008)

The use of hydrogen-bonding patterns in the same way as is known from DNA building blocks is a challenge for the construction of novel types of suitable chromophoric probes. This feature has been utilised for the construction of a novel type of UV/Vis probe for detection of supramolecular AAD or DAD sequences (A=hydrogen bond acceptor, D=hydrogen bond donor). Here we report on the structure of the enolisable chromophore 1-n-butyl-5-(4-nitrophenyl)barbituric acid (1), which has an adjustable hydrogen-bonding pattern. The position of the keto-enol equilibrium of this dye is strongly influenced both by the solvent polarity and by the chemical environment. Furthermore, the recognition properties of the barbiturate were examined by the use of seven artificial receptors: the pyridine bases 2,6-diaminopyridine (DAP), 2,6-diacetamidopyridine (DAC) and 2,6-bis(trifluoroacetamido)pyridine (TFA), as well as the nucleic acid bases 9-ethyladenine (EtAd), 9-ethylguanine (EtGu), 1-n-butylcytosine (BuCy) and 1-n-butylthymine (BuTy). It was found that 1 can interact with these bases either through acid-base interaction or by hydrogen-bonding complexation. The balance between the interactions is dependent both on the basicity strength and on the presence of a suitable recognition sequence in the base. The induced formation of the enol form of 1 thus causes a significant UV/Vis shift as function of the nature of the base.
Abstract 6073: The lipogenic regulator SREBP induces Transferrin in circulating melanoma cells, suppressing their susceptibility to ferroptosis (2020)

Abstract Circulating tumor cells (CTCs) are shed by cancers into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastatic outgrowth. Clonally derived cultured CTCs from patients with BRAF-mutant melanoma reveal upregulation of lipogenesis and iron homeostasis pathways, correlated with their baseline and acquired drug resistance. In CTCs, the lipogenesis regulator SREBP directly induces transcription of the iron carrier Transferrin (TF), thereby reducing intracellular reactive oxygen species (ROS) and lipid peroxidation, and conferring resistance to BRAF inhibitors and inducers of ferroptosis. Knockdown of endogenous TF impairs tumorigenesis by melanoma CTCs; their associated soft agar clonogenic defect is rescued by the lipophilic anti-oxidants Ferrostatin-1 or Vitamin E, and by cholesterol. Single cell RNA-seq of patient-derived melanoma CTCs identifies a subset with high lipogenic, iron metabolic and proliferative signatures, correlated with adverse clinical outcome. Together, the coordinated regulation of these SREBP-driven pathways contributes to cancer progression, drug resistance and metastasis. Citation Format: Xin Hong, Whijae Roh, Ryan J. Sullivan, Keith H. Wong, Ben S. Wittner, HongShan Guo, Taronish D. Dubash, Moshe Sade-Feldman, Ben K. Wesley, Genevieve M. Boland, Dieuwke L. Marvin, Todd Bonesteel, Chenyue Lu, Elad Horwitz, François Aguet, Samuel S. Freeman, Katherine Calhoun, Michelle K. Jewett, Linda T. Nieman, Nir Hacohen, Anders M. Näär, David T. Ting, Mehmet Toner, Shannon L. Stott, Gad Getz, Shyamala Maheswaran, Daniel A. Haber. The lipogenic regulator SREBP induces Transferrin in circulating melanoma cells, suppressing their susceptibility to ferroptosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6073.
Detection of Chromosomal Translocation in Hematologic Malignancies by a Novel DNA-Based Looped Ligation Assay (LOLA) (2017)

Our results indicate that LOLA is a simple method that is useful for DNA-based detection of translocations in challenging situations, particularly where the breakpoints are not tightly clustered. The assay also has the added benefit of permitting rapid mapping of the breakpoints.
Sphingosine Kinase 2 Is Required for Modulation of Lymphocyte Traffic by FTY720 (2005)

Immunotherapeutic drugs that mimic sphingosine 1-phosphate (S1P) disrupt lymphocyte trafficking and cause T helper and T effector cells to be retained in secondary lymphoid tissue and away from sites of inflammation. The prototypical therapeutic agent, 2-alkyl-2-amino-1,3-propanediol (FTY720), stimulates S1P signaling pathways only after it is phosphorylated by one or more unknown kinases. We generated sphingosine kinase 2 (SPHK2) null mice to demonstrate that this kinase is responsible for FTY720 phosphorylation and thereby its subsequent actions on the immune system. Both systemic and lymphocyte-localized sources of SPHK2 contributed to FTY720 induced lymphopenia. Although FTY720 was selectively activated in vivo by SPHK2, other S1P pro-drugs can be phosphorylated to cause lymphopenia through the action of additional sphingosine kinases. Our results emphasize the importance of SPHK2 expression in both lymphocytes and other tissues for immune modulation and drug metabolism.
A modular six-directional force sensor for prosthetic assessment: a technical note. (1997)

A device designed to measure the forces and moments transmitted through prostheses of persons with lower limb amputation is presented. The sensing unit design is an advancement over previous prosthesis force measurement devices in that it is very thin (19 mm) and lightweight (527.5 g, including signal-conditioning instrumentation). The disk-shaped transducer fits between the socket and socket adapter of a standard modular prosthesis, measuring all six force and moment components at this location. Twelve strain gages were used, configured into six two-arm active Wheatstone bridge circuits. A 6X6 matrix was constructed from calibration data to relate the 6-component bridge-output vector to a 6-component force and moment vector. In a bench-test setting, the sensor was evaluated under typical load combinations encountered during the walking of a person with transtibial amputation (TTA) and shown to have errors less than 7.2% of the full-scale output for each direction. Data collected on a subject with TTA walking at different speeds are presented.
Biomarkers, measured during therapy, for response of melanoma patients to immune checkpoint inhibitors: a systematic review (2019)

Immune checkpoint inhibitors (ICIs), which target CTLA-4 or PD-(L)1 molecules, have shown impressive therapeutic results. Durable responses, however, are only observed in a segment of the patient population and must be offset against severe off-target immune toxicity and high costs. This calls for biomarkers that predict response during ICI treatment. Although many candidate biomarkers exist, as yet, there has been no systematic overview of biomarkers predictive during. Here, we provide a systematic review of the current literature of ICI treatment to establish an overview of candidate predictive biomarkers during ICI treatment in melanoma patients. We performed a systematic Medline search (2000-2018, 1 January) on biomarkers for survival or response to ICI treatment in melanoma patients. We retrieved 735 publications, of which 79 were finally included in this systematic review. Blood markers were largely studied for CTLA-4 ICI, whereas tumor tissue markers were analyzed for PD-(L)1 ICI. Blood cytology and soluble factors were more frequently correlated to overall survival (OS) than response, indicating their prognostic rather than predictive nature. An increase in tumor-infiltrating CD8 + T-cells and a decrease in regulatory T-cells were correlated to response, in addition to mutational load, neoantigen load, and immune-related gene expression. Immune-related adverse events were also associated frequently with a favorable response and OS. This review shows the great variety of potential biomarkers published to date, in an attempt to better understand response to ICI therapy; it also highlights the candidate markers for future research. The most promising biomarkers for response to ICI treatment are the occurrence of immune-related adverse events (especially vitiligo), lowering of lactate dehydrogenase, and increase in activated CD8 + and decrease in regulatory T-cells.
Seeding R at sFLASH (2019)

Free-electron lasers (FELs) based on the self-amplified spontaneous emission (SASE) principle generate photon pulses with typically poor longitudinal coherence. FEL seeding techniques greatly improve longitudinal coherence by initiating FEL amplification in a controlled way using coherent light pulses. The sFLASH experiment installed at the FEL user facility FLASH at DESY in Hamburg is dedicated to the study of external seeding techniques. In this paper, the layout of the sFLASH seeding experiment is presented and an overview of recent developments is given.
Mutations in the Arabidopsis VAR2 locus cause leaf variegation due to the loss of a chloroplast FtsH protease (2000)

Variegated plants have green- and white-sectored leaves. Cells in the green sectors contain morphologically normal chloroplasts, whereas cells in the white sectors contain non-pigmented plastids that lack organized lamellar structures. Many variegations are caused by mutations in nuclear genes that affect plastid function, yet in only a few cases have the responsible genes been cloned. We show that mutations in the nuclear VAR2 locus of Arabidopsis cause variegation due to loss of a chloroplast thylakoid membrane protein that bears similarity to the FtsH family of AAA proteins (ATPases associated with diverse cellular activities). Escherichia coli FtsH is a chaperone metalloprotease that functions in a number of diverse membrane-associated events. Although FtsH homologs have been identified in multicellular organisms, their functions and activities are largely unknown; we provide genetic in vivo evidence that VAR2 functions in thylakoid membrane biogenesis. We have isolated four var2 alleles and they have allowed us to define domains of the protein that are required for activity. These include two putative ATP-binding sites. VAR2 protein amounts generally correlate with the severity of the var2 mutant phenotype. One allele lacks detectable VAR2 protein, suggesting that the mechanism of var2 variegation involves the action of a redundant activity in the green sectors. We conclude that redundant activities may be a general mechanism to explain nuclear gene-induced plant variegations.
Lack of Goal Attainment Regarding the Low-density Lipoprotein Cholesterol Level in the Management of Type 2 Diabetes Mellitus (2013)

Polydisease and polypharmacy issues in diabetes patients with a history of CAD constitute a growing barrier to medication adherence and the attainment of treatment goals.