gebhart/patrepeval huggingface dataset:
Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors (2004)

BACKGROUND: A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2)-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity. METHODS: C57BL/6 mice received subcutaneous (s.c.) vaccinations with bone marrow-derived dendritic cells (DCs) pulsed with synthetic peptides recognized by CD8+ (mEphA2671-679, mEphA2682-689) and CD4+ (mEphA230-44) T cells. Splenocytes (SPCs) were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL) responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6) establishment/progression was then assessed. RESULTS: Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA) peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models. CONCLUSIONS: These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells.
Sucrose Synthase Catalyzes the de novo Production of ADPglucose Linked to Starch Biosynthesis in Heterotrophic Tissues of Plants (2003)

By using barley seeds, developmental changes of ADPglucose (ADPG)-producing sucrose synthase (SS) and ADPG pyrophosphorylase (AGPase) have been compared with those of UDPglucose (UDPG), ADPG, sucrose (Suc) and starch contents. Both ADPG-synthesizing SS and AGPase activity patterns were found to correlate well with those of ADPG and starch contents. Remarkably, however, maximal activities of ADPG-synthesizing SS were found to be several fold higher than those of AGPase throughout seed development, the highest rate of starch accumulation being well accounted for by SS. Kinetic analyses of SS from barley endosperms and potato tubers in the Suc cleavage direction showed similar K(m) values for ADP and UDP, whereas apparent affinity for Suc was shown to be higher in the presence of UDP than with ADP. Moreover, measurements of transglucosylation activities in starch granules incubated with purified SS, ADP and [U-(14)C]Suc revealed a low inhibitory effect of UDP. The ADPG and UDPG contents in the transgenic S-112 SS and starch deficient potato mutant [Zrenner et al. (1995) Plant J. 7: 97] were found to be 35% and 30% of those measured in wild-type plants, whereas both glucose-1-phosphate and glucose-6-phosphate contents were found to be normal as compared with those of wild-type plants. The overall results thus strongly support a novel gluconeogenic mechanism reported previously [Pozueta-Romero et al. (1999) CRIT: Rev. Plant Sci. 18: 489] wherein SS catalyses directly the de novo production of ADPG linked to starch biosynthesis in heterotrophic tissues of plants.
An asymmetrical lightly-doped source (ALDS) cell for virtual ground high density EPROMs (2003)

A novel EPROM (erasable programmable read-only memory) cell structure with asymmetrically doped source and drain junction suitable for virtual ground array architecture is described. The asymmetric cell nature eliminates a write disturbance of the adjacent cell in the write mode. In the read mode, the cell provides higher read current and substantial soft-write lifetime as a result of the selection of the lightly doped n/sup -/ region as the drain. The cell is implemented in virtual ground designs. A novel planarized process has been developed to improve the manufacturability. It is concluded that such scalable cell and array structures are promising for the next-generation high-density EPROMs in the 16-Mb regime.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Induction of DISE in ovarian cancer cells in vivo (2017)

The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. shRNAs and siRNAs derived from CD95 or CD95 ligand (CD95L) are highly toxic to most cancer cells. We recently found that these sh/siRNAs kill cancer cells in the absence of the target by targeting the 3'UTRs of critical survival genes through canonical RNAi. We have named this unique form of off-target effect DISE (for death induced by survival gene elimination). DISE preferentially kills transformed cells and cancer stem cells. We demonstrate that DISE induction occurs in cancer cells <i>in vivo</i> after introducing a lentiviral CD95L derived shRNA (shL3) into HeyA8 ovarian cancer cells grown as i.p. xenografts in mice, when compared to a scrambled shRNA. To demonstrate the possibility of therapeutically inducing DISE, we coupled siRNAs to templated lipoprotein nanoparticles (TLP). <i>In vitro</i>, TLPs loaded with a CD95L derived siRNA (siL3) selectively silenced a biosensor comprised of Venus and CD95L ORF and killed ovarian cancer cells. <i>In vivo</i>, two siRNA-TLPs (siL2-TLP and siL3-TLP) reduced tumor growth similarly as observed for cells expressing the shL3 vector. These data suggest that it is possible to kill ovarian cancer cells <i>in vivo</i> via DISE induction using siRNA-TLPs.
The Effect of Ocular Pigmentation on Transscleral Delivery of Triamcinolone Acetonide (2013)

TA can bind to and release from the ocular pigment, which may extend the TA ocular half-life and therapeutic duration when TA is delivered through a subtenon injection. A further in vivo study is warranted to validate the findings and to quantitate the magnitude of the difference between pigmented and albino animals.
Providing a Linux API on the Scalable K42 Kernel. (2003)

K42 is an open-source research kernel targeted for 64bit cache-coherent multiprocessor systems. It was designed to scale up to multiprocessor systems containing hundreds or thousands of processors and to scale down to perform well on 2to 4-way multiprocessors. K42’s goal was to re-design the core of an operating system, but not an entire application environment. We wanted to use a commonly available interface with a large established code base. Because Linux is open source and widely available, we chose to support its application environment by supporting the Linux API and ABI. There were some interesting complications as well as advantages that arose from K42’s structure because our implementation of the Linux application environment was done primarily in user space, had to interface with K42’s object-oriented technology, and used fine-grained locking. Other research systems efforts directed at achieving a high degree of scalability and maintainability exhibit similar structural characteristics. In this paper we present the motivation behind K42, including its goals and overall structure, and describe its system interface. We then focus on the required infrastructure and mechanisms needed to efficiently support a Linux application environment. We examine the lessons learned of what was advantageous and what was disadvantageous from K42 in implementing the Linux API and ABI.
Muscle Wasting and Resistance of Muscle Anabolism: The “Anabolic Threshold Concept” for Adapted Nutritional Strategies during Sarcopenia (2012)

Skeletal muscle loss is observed in several physiopathological situations. Strategies to prevent, slow down, or increase recovery of muscle have already been tested. Besides exercise, nutrition, and more particularly protein nutrition based on increased amino acid, leucine or the quality of protein intake has generated positive acute postprandial effect on muscle protein anabolism. However, on the long term, these nutritional strategies have often failed in improving muscle mass even if given for long periods of time in both humans and rodent models. Muscle mass loss situations have been often correlated to a resistance of muscle protein anabolism to food intake which may be explained by an increase of the anabolic threshold toward the stimulatory effect of amino acids. In this paper, we will emphasize how this anabolic resistance may affect the intensity and the duration of the muscle anabolic response at the postprandial state and how it may explain the negative results obtained on the long term in the prevention of muscle mass. Sarcopenia, the muscle mass loss observed during aging, has been chosen to illustrate this concept but it may be kept in mind that it could be extended to any other catabolic states or recovery situations.
Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials (2012)

There remain some key questions regarding the adoptive infusion of chimeric antigen receptor (CAR) transduced T-cells in the clinical setting. This article systematically reviews the phase I clinical trials using CARs targeting CD19 in B-lineage malignancies. Twenty-nine patients were enrolled and the 6-month progression free survival for this cohort was 50.0 ± 9.9%. Univariate analysis showed that patients benefited from lymphodepletion before CAR+T-cell infusion and the administration of interleukin-2 (IL-2). Longer-term persistence (≥ 4 weeks) and stronger expansion of CAR+ T-cells in the blood and higher peak serum interferon-γ (IFN-γ) level (≥ 200 pg/mL) were also related to superior outcome. Regarding treatment-related adverse events, the most prominent toxicities were fever, rigors, chills, acute renal failure, hypotension and capillary leak syndrome. In conclusion, anti-CD19 CAR+ T-cells have shown some benefits in patients with B-lineage malignancies and are well tolerated in most patients. Preconditioning and cytokine supplement are required to improve the clinical outcome.
Multipath delay spread in a hilly region at 210 MHz (1987)

Investigations of multipath propagation in hilly terrain show that the delay spread between the first and the last significant path may be greater than 30µs. The method of measurement is described, and the propagation conditions are illustrated by representative examples.
Thymic carcinoma: A rare cancer requiring special attention (2011)

Thymic carcinoma is a rare but highly aggressive, easily metastasizing cancer derived from thymic epithelial cells and has a very poor prognosis. Unlike thymoma, which is usually found because it is associated with paraneoplastic syndrome, thymic carcinoma is almost always found at an advanced stage because patients often have atypical symptoms. There is no known tumor marker for thymic carcinoma screening. Because most tumors are discovered at an advanced stage, the Masaoka staging system, which is widely used for thymoma, is of questionable value for thymic carcinoma. Complete resection of the tumor is the mainstay of treatment and leads to the best survival rate for patients. However, the complete resection rate is only approximately 50% and the recurrence rate after complete resection is high, up to 40%. The role of postoperative radiotherapy or chemotherapy is still controversial. For tumors that cannot be completely resected, the result of debulking surgery is not different from that of a biopsy. The efficacy of preoperative radiotherapy, chemotherapy, or concurrent chemoradiation therapy is still debatable because most studies on these topics were for only a small number of patients and were retrospective in nature. The overall 5-year survival rate for patients with thymic carcinoma is only 30–50%. A prospective randomized study requires multi-center collaboration and the establishment of an optimal treatment protocol to increase the survival rate of patients with thymic carcinoma, for which there is no predictive screening biomarker or a suitable staging system at present.
Long peptides induce polyfunctional T cells against conserved regions of HIV‐1 with superior breadth to single‐gene vaccines in macaques (2010)

A novel T-cell vaccine strategy designed to deal with the enormity of HIV-1 variation is described and tested for the first time in macaques to inform and complement approaching clinical trials. T-cell immunogen HIVconsv, which directs vaccine-induced responses to the most conserved regions of the HIV-1, proteome and thus both targets diverse clades in the population and reduces the chance of escape in infected individuals, was delivered using six different vaccine modalities: plasmid DNA (D), attenuated human (A) and chimpanzee (C) adenoviruses, modified vaccinia virus Ankara (M), synthetic long peptides, and Semliki Forest virus replicons. We confirmed that the initial DDDAM regimen, which mimics one of the clinical schedules (DDDCM), is highly immunogenic in macaques. Furthermore, adjuvanted synthetic long peptides divided into sub-pools and delivered into anatomically separate sites induced T-cell responses that were markedly broader than those elicited by traditional single-open-reading-frame genetic vaccines and increased by 30% the overall response magnitude compared with DDDAM. Thus, by improving both the HIV-1-derived immunogen and vector regimen/delivery, this approach could induce stronger, broader, and theoretically more protective T-cell responses than vaccines previously used in humans.
Multiplication of cellular radio capacity by blind adaptive spatial filtering (2003)

A scheme for cellular radio which greatly increases the allowable number of simultaneous users in each cell is proposed. The scheme employs space-division multiplexing by means of an adaptive antenna array at the base station (1) to separate the temporally and spectrally overlapping signals of users that arrive from different locations within the cell and to mitigate multipath fading and shadowing at the base station and (2) by reciprocity to transmit directively to minimize interfering signals arriving at the mobile units and to mitigate multipath fading and shadowing at the mobile units. A novel aspect of the proposed scheme is that no training signals are required for adaptation, nor are computationally intensive direction-finding methods required, nor is any calibration data required for the array. Results from computer simulations on the performance of the new scheme show that the proposed scheme can accommodate up to five times as many users as a proposed CDMA scheme using the same system bandwidth.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Control of Superhydrophilicity and Superhydrophobicity of a Superwetting Silicon Nanowire Surface (2010)

The superwetting or dewetting properties of a silicon nanowire (SiNW) surface are studied. The SiNW arrays were grown vertically on or Si substrates by a vapor–liquid–solid process. After a critical length or roughness, the nanowire surface exhibits superhydrophilic property with a contact angle close to 0°. However, the superhydrophilicity of the surface can be transformed into superhydrophobicity by a vacuum treatment, which is a low pressure diffusion process by the vapor from the polydimethylsiloxane material. In addition, the superhydrophobicity of the surface can be readily reversed back to superhydrophilicity by anneal with gas flow. The reverse nature of surface wettability can be repeated for many cycles by alternating vacuum with thermal treatment. Physical explanation together with analytical measurements are provided and discussed. The findings have opened a door to completely control the superhydrophilicity or superhydrophobicity of a surface with a very simple and cheap method.
Tracking epigenetic histone modifications in single cells using Fab-based live endogenous modification labeling (2011)

Histone modifications play an important role in epigenetic gene regulation and genome integrity. It remains largely unknown, however, how these modifications dynamically change in individual cells. By using fluorescently labeled specific antigen binding fragments (Fabs), we have developed a general method to monitor the distribution and global level of endogenous histone H3 lysine modifications in living cells without disturbing cell growth and embryo development. Fabs produce distinct nuclear patterns that are characteristic of their target modifications. H3K27 trimethylation-specific Fabs, for example, are concentrated on inactive X chromosomes. As Fabs bind their targets transiently, the ratio of bound and free molecules depends on the target concentration, allowing us to measure changes in global modification levels. High-affinity Fabs are suitable for mouse embryo imaging, so we have used them to monitor H3K9 and H3K27 acetylation levels in mouse preimplantation embryos produced by in vitro fertilization and somatic cell nuclear transfer. The data suggest that a high level of H3K27 acetylation is important for normal embryo development. As Fab-based live endogenous modification labeling (FabLEM) is broadly useful for visualizing any modification, it should be a powerful tool for studying cell signaling and diagnosis in the future.
Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. (1985)

The major isoenzymes of cytosolic glutathione transferase (EC 2.5.1.18) from rat, mouse, and man are shown to share structural and catalytic properties that can be used for species-independent classification. Rat, mouse, and human isoenzymes were grouped with respect to amino-terminal amino acid sequences, after correlation of seven structures analyzed in the present investigation with structures determined earlier. The isoenzymes were also characterized by substrate specificities and sensitivities to inhibitors, and the data were subjected to pattern recognition analysis. In addition, the various isoenzymes were tested for cross-reactivity by immunoprecipitation with antibodies raised against rat and human transferases. The different types of data were clearly correlated and afforded an unambiguous division of the isoenzymes into three classes named alpha, mu, and pi. Each of the three mammalian species studied contains at least one isoenzyme of each class. It is suggested that the similarities of the isoenzymes in a class reflect evolutionary relationships and that the classification applies generally.
Rat immunogenicity assay of inactivated poliovirus. (1996)

A rat immunogenicity assay for IPV potency was validated and applied to routine vaccine testing as a potential alternative to the CFR Monkey Potency Assay. Potencies of pure trivalent polio, various combinations and experimental vaccines were tested with a view of producing a single dilution assay.
Combined Targeting of Costimulatory (OX40) and Coinhibitory (CTLA-4) Pathways Elicits Potent Effector T Cells Capable of Driving Robust Antitumor Immunity (2013)

Ligation of the TNF receptor family costimulatory molecule OX40 (CD134) with an agonist anti-OX40 monoclonal antibody (mAb) enhances antitumor immunity by augmenting T-cell differentiation as well as turning off the suppressive activity of the FoxP3(+)CD4(+) regulatory T cells (Treg). In addition, antibody-mediated blockade of the checkpoint inhibitor CTLA-4 releases the "brakes" on T cells to augment tumor immunotherapy. However, monotherapy with these agents has limited therapeutic benefit particularly against poorly immunogenic murine tumors. Therefore, we examined whether the administration of agonist anti-OX40 therapy in the presence of CTLA-4 blockade would enhance tumor immunotherapy. Combined anti-OX40/anti-CTLA-4 immunotherapy significantly enhanced tumor regression and the survival of tumor-bearing hosts in a CD4 and CD8 T cell-dependent manner. Mechanistic studies revealed that the combination immunotherapy directed the expansion of effector T-bet(high)/Eomes(high) granzyme B(+) CD8 T cells. Dual immunotherapy also induced distinct populations of Th1 [interleukin (IL)-2, IFN-γ], and, surprisingly, Th2 (IL-4, IL-5, and IL-13) CD4 T cells exhibiting increased T-bet and Gata-3 expression. Furthermore, IL-4 blockade inhibited the Th2 response, while maintaining the Th1 CD4 and effector CD8 T cells that enhanced tumor-free survival. These data demonstrate that refining the global T-cell response during combination immunotherapy can further enhance the therapeutic efficacy of these agents.
Cloning of plasmid DNA sequences involved in invasion of HeLa cells by Shigella flexneri (1985)

A large plasmid is found in virulent isolates of Shigella sp. and encodes functions essential for invasion of mammalian cells. To identify plasmid sequences necessary for invasion, we isolated a series of Tn5 insertions in pWR100, the virulence plasmid of Shigella flexneri serotype 5. These insertions demonstrated that three separate EcoRI fragments of pWR100 were required for invasion of HeLa cells. However, the corresponding native EcoRI fragments, when cloned into pBR325, did not restore virulence to plasmidless strains. Construction of a lambda-sensitive, plasmidless Shigella recipient enabled us to shotgun clone plasmid DNA directly into S. flexneri by using the cosmid vector pJB8 and score for expression of invasive functions. In this fashion, we succeeded in isolating six independent recombinants which restored invasion of HeLa cells in plasmidless Shigella recipients. The cloned inserts all contained a common core of ca. 37 kilobases, thus defining a minimum sequence necessary for invasion of HeLa cells. Virulence-associated peptides produced by wild-type S. flexneri were also produced by the recombinants. Expression of these peptides and expression of invasiveness by the clones were regulated by growth temperature, as is expression of these traits in wild-type S. flexneri. A complete invasive phenotype was not expressed by the recombinants in that they failed to produce a positive Sereny test. Possible explanations for this behavior as it relates to the mechanism of bacterial invasion are discussed.
A QoS-aware memory controller for dynamically balancing GPU and CPU bandwidth use in an MPSoC (2012)

Diverse IP cores are integrated on a modern system-on-chip and share resources. Off-chip memory bandwidth is often the scarcest resource and requires careful allocation. Two of the most important cores, the CPU and the GPU, can both simultaneously demand high bandwidth. We demonstrate that conventional quality-of-service allocation techniques can severely constrict GPU performance by allowing the CPU to occasionally monopolize shared bandwidth. We propose to dynamically adapt the priority of CPU and GPU memory requests based on a novel mechanism that tracks progress of GPU workloads. Our evaluation shows that the proposed mechanism significantly improves GPU performance with only minimal impact on the CPU.