gebhart/patrepeval huggingface dataset:
Detecting neoepitope-specific intra-tumoral T cell responses in a glioblastoma patient treated with personal neoantigen vaccine (2018)

Abstract Recent advances in single cell T cell receptor (TCR) sequencing have allowed detailed analysis of TCRαβ pairs. However, efficient methods for probing the specificity of discovered TCRs remain limited. We developed a streamlined approach for cloning and expressing TCRs and screening against candidate antigens. A key innovation was the establishment of a plasmid library to encode all variable (V) regions of the TCR, from which any TCR of interest can be assembled with only custom synthesis of short CDR3 regions. A reporter cell system allows rapid detection of TCR antigen specificity and assessment of functional avidity based on cytokine production. We applied this pipeline to study the intra-tumoral TCR repertoire of a patient with glioblastoma treated with personal neoantigen vaccine. The vaccine consisted of up to 20 synthetic long peptides containing predicted neoepitopes and poly-ICLC adjuvant. Single cell TCR sequencing of CD3+ tumor infiltrating lymphocytes (TILs) and peripheral T cells in vitro expanded against immunizing peptides showed that 4 CD4+ and 2 CD8+ T cell clonotypes in peripheral blood were identical to TILs. The cloning and expression system was used to test their specificity. We identified a TCR from a CD4+ TIL specific for ARHGAP35, a neoantigen targeted by vaccination, and capable of discriminating between mutant and wildtype peptide. This result provides the first demonstration that neoepitope-sensitized T cells can traffic from the periphery to an intracranial GBM. Overall, we demonstrated our ability to identify TCRαβ pairs, express them on demand, and probe antigen specificity. Ongoing studies are characterizing the functional avidity of neoepitope-specific TCRs and reactivity against autologous tumor.
Dynamic simulation of deformable objects using the Long Elements Method (2003)

This paper presents the Long Elements Method - LEM, a new method for real time, physically based, dynamic simulation of deformable objects. The method is based on a new meshing strategy, using long elements. The number of elements per model is proportional to the square of the length of a side rather than its cube as in a standard meshing based in cubes or tetrahedra. The LEM uses an original combination of static (state-less) and dynamic approaches to simulate deformations and dynamics. Global deformations that conserve volume and are convincingly compliant are obtained. Models are defined using bulk material properties. The method is particularly attractive for soft tissue modeling.
Inhibition of EBV-Induced Lymphoproliferation by CD4+ T Cells Specific for an MHC Class II Promiscuous Epitope (2002)

Posttransplant lymphoproliferative disorder (PTLD) and B cell lymphomas induced by EBV continue to be a major life-threatening complication in transplant patients. The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish these complications, but the lack of an effective vaccine has limited this prophylactic approach. We describe here the identification of a peptide epitope from the EBV EBNA2 Ag that is capable of inducing in vitro CD4(+) T cell responses that inhibit the EBV-mediated B lymphocyte proliferation associated with PTLD. Most significantly, T cell responses to the EBNA2 epitope were found to be restricted by numerous MHC class II alleles (DR1, DR7, DR16, DR52, DQ2, and DQ7), indicating that this peptide is highly promiscuous and would be recognized by a large proportion (>50%) of the general population. These results are relevant for the design of a simple, inexpensive and widely applicable peptide-based vaccine to prevent PTLD in solid organ transplant patients.
Word Sense Disambiguation with Automatically Acquired Knowledge (2010)

This article describes an automatic word sense disambiguation method—determining which word sense fits in a given context—that makes the process feasible in practice.
Design, fabrication, and tests of a metallic shell tile thermal protection system for space transportation (1989)

A thermal protection tile for earth-to-orbit transports is described. The tiles consist of a rigid external shell filled with a flexible insulation. The tiles tend to be thicker than the current Shuttle rigidized silica tiles for the same entry heat load but are projected to be more durable and lighter. The tiles were thermally tested for several simulated entry trajectories.
III-Nitride transistors with photonic-ohmic drain for enhanced dynamic performances (2015)

Development of III-nitride high-voltage power devices is still challenged by deep traps that are inevitable in state-of-the-art AlGaN/GaN-on-Si epitaxial heterostructures. In this work, we report a heterojunction field-effect transistor featuring a photonic-ohmic drain, i.e. PODFET, on conventional AlGaN/GaN-on-Si power electronics platform. Photons are synchronously generated with the switching channel current, and they are capable of effectively pumping electrons from the deep surface/bulk traps during each switching cycle. Consequently, the dynamic ON-resistance of the PODFET is significantly reduced compared to that of a conventional ohmic-drain FET.
Metal Artifact Reduction in CT: Where Are We After Four Decades? (2016)

Methods to overcome metal artifacts in computed tomography (CT) images have been researched and developed for nearly 40 years. When X-rays pass through a metal object, depending on its size and density, different physical effects will negatively affect the measurements, most notably beam hardening, scatter, noise, and the non-linear partial volume effect. These phenomena severely degrade image quality and hinder the diagnostic power and treatment outcomes in many clinical applications. In this paper, we first review the fundamental causes of metal artifacts, categorize metal object types, and present recent trends in the CT metal artifact reduction (MAR) literature. To improve image quality and recover information about underlying structures, many methods and correction algorithms have been proposed and tested. We comprehensively review and categorize these methods into six different classes of MAR: metal implant optimization, improvements to the data acquisition process, data correction based on physics models, modifications to the reconstruction algorithm (projection completion and iterative reconstruction), and image-based post-processing. The primary goals of this paper are to identify the strengths and limitations of individual MAR methods and overall classes, and establish a relationship between types of metal objects and the classes that most effectively overcome their artifacts. The main challenges for the field of MAR continue to be cases with large, dense metal implants, as well as cases with multiple metal objects in the field of view. Severe photon starvation is difficult to compensate for with only software corrections. Hence, the future of MAR seems to be headed toward a combined approach of improving the acquisition process with dual-energy CT, higher energy X-rays, or photon-counting detectors, along with advanced reconstruction approaches. Additional outlooks are addressed, including the need for a standardized evaluation system to compare MAR methods.
Heterologous protein expression in the methylotrophic yeast<i>Pichia pastoris</i> (2000)

During the past 15 years, the methylotrophic yeast Pichia pastoris has developed into a highly successful system for the production of a variety of heterologous proteins. The increasing popularity of this particular expression system can be attributed to several factors, most importantly: (1) the simplicity of techniques needed for the molecular genetic manipulation of P. pastoris and their similarity to those of Saccharomyces cerevisiae, one of the most well-characterized experimental systems in modern biology; (2) the ability of P. pastoris to produce foreign proteins at high levels, either intracellularly or extracellularly; (3) the capability of performing many eukaryotic post-translational modifications, such as glycosylation, disulfide bond formation and proteolytic processing; and (4) the availability of the expression system as a commercially available kit. In this paper, we review the P. pastoris expression system: how it was developed, how it works, and what proteins have been produced. We also describe new promoters and auxotrophic marker/host strain combinations which extend the usefulness of the system.
Eμ- <i>TCL1</i> mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction (2009)

Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-cell function in the chronic lymphocytic leukemia (CLL) Emu-TCL1 transgenic mouse model. With development of leukemia, Emu-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients. Furthermore, infusion of CLL cells into young Emu-TCL1 mice induced defects comparable to those seen in mice with developed leukemia, demonstrating a causal relationship between leukemia and the T-cell defects. Altered pathways involved genes regulating actin remodeling, and T cells exhibited dysfunctional immunological synapse formation and T-cell signaling, which was reversed by the immunomodulatory drug lenalidomide. These results further demonstrate the utility of this animal model of CLL and define a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.
A Sealed System and Compressor Model for Optimal Control of Household Refrigerators (2012)

Increasingly stringent industry standards have posed significant challenges on manufacturers to enhance the design and performance of household refrigerators. One of the least expensive and most effective means of improving the system is optimizing the control strategy. Some of the most promising control systems, such as adaptive and optimal control methods, require an accurate model of the system to guide the control effort. However, the complexity and interconnectedness of thermal and refrigerant flow phenomena make developing modern control systems a particularly challenging aspect of designing refrigerators, in spite of many decades of research and development. There exist models to correlate the desired compartments’ temperatures to that of the evaporator coil. However, there is a lack of a general approach to translate the required evaporator temperature to a compressor speed that provides it in an energy efficient manner. This work introduces a method to make that connection. The technique developed in this work can be adjusted for implementation on various refrigerator sizes and platforms to help modulate and control the compressor speed in real time.
Virtual DBA: virtualizing passive optical networks to enable multi-service operation in true multi-tenant environments (2020)

This paper presents the concept of virtual dynamic bandwidth allocation (DBA), a method we propose to virtualize upstream capacity scheduling in passive optical networks (PONs), which provides multiple independent virtual network operators with the ability to precisely schedule their upstream traffic allocation. After a brief introduction on the evolution of access network sharing, we present our virtual DBA architecture, detailing its main components. We then provide a summary of the work done in this area from both theoretical and practical implementation perspectives. In this paper, we propose a novel stateless algorithm for merging multiple independent virtual bandwidth maps based on priority classes and analyze its performance in terms of efficiency of capacity allocation and latency. Through our results, we discuss the existence of a trade-off between traffic load and grant size distribution versus efficiency and latency. We find that, different from a residential single-tenant application, when PONs are used for low-latency and multi-tenant applications, the system has better overall performance if grants are allocated in small size. In addition, our analysis shows that for high-priority, strict latency services, our proposed merging algorithm presents delay performance that is independent of the traffic distribution considered.
Nano-mupirocin: enabling the parenteral activity of mupirocin (2016)

Abstract Mupirocin is an antibiotic having a unique mode of action, not shared by any other therapeutically available antibiotic. However, due to its rapid elimination following injection and high protein binding, current therapeutic use is limited to topical administration. Computational methods have identified mupirocin as a good candidate for delivery via long-circulating nano-liposomes. Formulating mupirocin in such liposomes to form Nano-mupirocin protects the drug in the circulation, enabling therapeutic efficacy. This was demonstrated using two different animal models that served as a proof of concept: the mice necrotizing fasciitis and rabbit endocarditis models. In both animal models, mupirocin administered intravenously (IV) lacked therapeutic efficacy, while the Nano-mupirocin administered IV was efficacious. In both mice and rabbits the pharmacokinetic (PK) profile following IV injection of Nano-mupirocin showed significantly greater AUC and elimination half-life of Nano-mupirocin compared to the free drug. In addition, in mice we also demonstrated significant drug distribution into the disease site. These PK profiles may explain Nano-mupirocin’s superior therapeutic efficacy. To the best of our knowledge, this is the first study demonstrating that systemic activity of mupirocin is feasible. Therefore, Nano-mupirocin can be considered a novel and unique parenteral antibiotic candidate drug.
Development of Novel Anti-agglomerant Chemistries with Reduced Localized Corrosion Potential to Stainless and Duplex Steels (2015)

Abstract Low dosage hydrate inhibitors (LDHIs) have been used as alternatives to thermodynamic inhibitors such as methanol or mono ethylene glycol (MEG) to control hydrate problems. The major advantage of using LDHIs is that they control with a much lower dosage, typically 1 to 3vol% (based on water production volume), thus lowering storage requirements and logistical challenges, compared to much higher volumes required for methanol or MEG. Anti-agglomerants (AAs), as one type of LDHI, allow hydrates to form but inhibit growth and agglomeration of hydrate crystals. Some very effective AAs exhibit a pitting corrosion risk for offshore umbilical chemical delivery systems under certain conditions. An electrochemical method of cyclic potentiodynamic polarization (CPP), a modified ASTM G-61 method at ambient temperature, and immersion testing using a modified ASTM G-31 method at elevated temperatures were used to evaluate pitting tendencies of AA formulations containing corrosion inhibitors on stainless and duplex steels. Initially, these corrosion inhibitors were effective in controlling pitting corrosion in stainless steel only as shown by CPP and immersion testing. After modifying the manufacturing process and adjusting solvent systems, the selected corrosion inhibitors have been shown to be effective for both stainless and duplex steels. Hydrate performance testing showed no performance compromise with the presence of corrosion inhibitors within the AA formulation or from changing the solvent system. Mitigation of pitting tendency was also confirmed by immersion testing at elevated temperatures.
Chemical and Clinical Development of Darinaparsin, a Novel Organic Arsenic Derivative (2008)

The inorganic arsenic derivative arsenic trioxide (ATO) has proven to be highly efficacious in patients with acute promyelocytic leukemia (APL) and has been associated with complete cytogenetic response in most treated patients diagnosed with this disease. This is due to ATO's direct effect on PML-RARalpha oncoprotein patognomonic for APL. ATO has shown moderate activity against certain other hematologic and solid organ malignancies but is also associated with significant toxicities, especially when used at higher doses. The development of orally bioavailable organic arsenic derivatives (OAD) offering improved toxicity profiles and better efficacy may expand the use of arsenic derivatives in hematologic malignancies and solid tumors. The favorable in vivo carcinostatic activity of S-dimethylarsino-thioglucose, the first OAD synthesized in murine leukemia models by our group in 1975, set the stage for our efforts to develop OADs. Unfortunately, the program remained dormant for almost two decades. The success of ATO in APL in the late 1990s re-ignited the interest in the use of OADs in cancer chemotherapy. This review describes the chemical development of OADs and summarizes the clinical development of a promising lead compound, Darinaparsin (ZIO-101; SGLU; S-dimethylarsino-glutathione), for the treatment of a variety of cancers.
Chemical characterization of thymosin beta 4. (1982)

As part of our ongoing investigations on the endocrine thymus, we have isolated and purified to homogeneity a hormone-like peptide which we have termed thymosin beta 4. Thymosin beta 4 has Mr = 4982 and an isoelectric point of 5.1. The complete amino acid sequence of this polypeptide has been established by automated Edman degradation as well as by manual sequence analysis. Thymosin beta 4 is composed of 43 amino acid residues with acetylserine at the NH2 terminus. This molecule induces expression of terminal deoxynucleotidyl transferase in transferase-negative murine thymocytes in vivo and in vitro. It also exhibits ability to inhibit the migration of macrophages. Comparison of the sequence of thymosin beta 4 to other thymic hormones or other published protein sequences does not reveal any statistically significant relationship. Two helical regions were identified in the structure using data for prediction of protein conformation. It is proposed that thymosin beta 4 is one of the biologically active peptides present in thymosin fractions 5 and 5A which participate in the regulation, differentiation, and function of thymus-derived lymphocytes and may also act directly or indirectly on macrophages and perhaps other cells involved in cell-mediated immunity.
FingerSight: Fingertip Haptic Sensing of the Visual Environment (2014)

We present a novel device mounted on the fingertip for acquiring and transmitting visual information through haptic channels. In contrast to previous systems in which the user interrogates an intermediate representation of visual information, such as a tactile display representing a camera generated image, our device uses a fingertip-mounted camera and haptic stimulator to allow the user to feel visual features directly from the environment. Visual features ranging from simple intensity or oriented edges to more complex information identified automatically about objects in the environment may be translated in this manner into haptic stimulation of the finger. Experiments using an initial prototype to trace a continuous straight edge have quantified the user's ability to discriminate the angle of the edge, a potentially useful feature for higher levels analysis of the visual scene.
Future of photorefractive based holographic 3D display (2009)

The very first demonstration of our refreshable holographic display based on photorefractive polymer was published in Nature early 2008<sup>1</sup>. Based on the unique properties of a new organic photorefractive material and the holographic stereography technique, this display addressed a gap between large static holograms printed in permanent media (photopolymers) and small real time holographic systems like the MIT holovideo. Applications range from medical imaging to refreshable maps and advertisement. Here we are presenting several technical solutions for improving the performance parameters of the initial display from an optical point of view. Full color holograms can be generated thanks to angular multiplexing, the recording time can be reduced from minutes to seconds with a pulsed laser, and full parallax hologram can be recorded in a reasonable time thanks to parallel writing. We also discuss the future of such a display and the possibility of video rate.
Broadcast-Based Peer-to-Peer Collaborative Video Streaming Among Mobiles (2007)

In traditional mobile streaming networks such as 3G cellular networks, all users pull streams from a server. Such pull model leads to high streaming cost and problem in system scalability. In this paper, we propose and investigate a fully distributed, scalable, and cost-effective protocol to distribute multimedia content to mobiles in a peer-to-peer manner. Our protocol, termed Collaborative Streaming among Mobiles (COSMOS), makes use of broadcasting and data sharing to achieve high performance (in terms of delay, cost fairness, stream continuity, etc.). In COSMOS, only a few peers pull video descriptions from base stations. Using a free broadcast channel (such as Wi-Fi and Bluetooth), they share the streams to nearby neighbors. As a result, COSMOS greatly reduces the streaming cost and cellular bandwidth requirement. Furthermore, as video streams are supplied by multiple peers, COSMOS is robust to peer failure. Since broadcasting is used to distribute video data, COSMOS is highly scalable to large number of users. In COSMOS, peers autonomously determine whether to broadcast packets or not in order to efficiently use of the channel bandwidth. By taking turns to pull descriptions, peers can effectively share, and hence substantially reduce, streaming cost. As broadcast scope is small and peers can often obtain a number of streams from its neighbors, COSMOS achieves low delay and excellent stream continuity
17.2: Large‐scale Color Omnidirectional‐view Three‐dimensional Display Based on Projector Array (2012)

Abstract Combining the characteristic of autostereoscopic and volumetric displays, large‐scale omnidirectional‐view three‐dimensional (3D) display utilizes projector array and cylindrical selective‐diffusing screen to reconstruct 3D light field. Large‐scale color omnidirectional‐view 3D display without any mechanical moving component is implemented. This paper presents principle of this method and analyzes display characteristics.
A segregation index combining phenotypic (clinical characteristics) and genotypic (gene expression) biomarkers from a urine sample to triage out patients presenting with hematuria who have a low probability of urothelial carcinoma (2015)

The adoption of G + P INDEX enables a significant change in clinical utility. G + P INDEX can be used to segregate hematuria patients with a low probability of UC with a high degree of confidence in the primary evaluation. Triaging out low-probability patients early significantly reduces the need for expensive and invasive work-ups, thereby lowering diagnosis-related adverse events and costs.