gebhart/patrepeval huggingface dataset:
CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network (2013)

Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs) and tumor dendritic cells (TuDCs) are the main protagonists of tumor-infiltrating lymphocyte (TIL) immunosuppression. TAMs have been widely investigated and are associated with poor prognosis, but the immunosuppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immunosuppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8(+) T cell receptor transgenic T cells (OTI) but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.
Missense Mutations in the Rod Domain of the Lamin A/C Gene as Causes of Dilated Cardiomyopathy and Conduction-System Disease (1999)

Genetic defects in distinct domains of the nuclear-envelope proteins lamin A and lamin C selectively cause dilated cardiomyopathy with conduction-system disease or autosomal dominant Emery-Dreifuss muscular dystrophy. Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.
Somatic and germinal inheritance of an FLP-mediated deletion in transgenic tobacco (1999)

Site-specific recombinases are increasingly being used in transgenic plants to engineer genetic rearrangements such as the removal of unwanted selectable markers and the activation or delation of expressed genes. Here a convenient vector system for the activation of transgene expression by FLP-mediated deletion of a transcription blocking sequence is presented. To investigate somatic and germinal transmission of deletion/activation events in transgenic tobacco (Nicotiana tabacum L. var. Xanthi) a derivative of this vector was constructed in which a spectinomycin resistance (SPEC) gene was introduced into plants in a silent state, separated from a CaMV 35S promoter by a GUS gene blocking sequence flanked by FLP target sites (FRTs). SPEC can therefore be activated by FLP-mediated excision of GUS. After crossing to appropriate FLP-expressing plants, heat-shock-induced FLP expression efficiently generated sectors of spectinomycin-resistant tobacco tissue. Constitutive expression of FLP resulted in activation of SPEC and loss of GUS activity in most somatic tissues of all plants carrying 35S-FLP and the target construct. One of the eight plants tested tramsmitted the recombined state to all progeny, indicative of excision activity in germinal tissue.
The Chromatography of Insulin on Deae-Cellulose in Buffers Containing 8m Urea (1960)

The chromatography of four samples of insulin by elution analysis at con· stant pH and ionic strength on a diethylaminoethyl (DEAE).cellulose column has been studied. The presence of three components was apparent at pH 7·4 in a buffer containing 8M urea. The results are compared with those obtained on the same samples of insulin by other workers using countercurrent and chromatographic techniques. The experimental and theoretical curves for the major peak of the International standard insulin sample coincide.
A Small Microwave Plasma Source for Long Column Production without Magnetic Field (1975)

A new HF device is described. It allows the production, without the use of a magnetic field, of long plasma columns from a small HF coupling structure situated at one end of the column. Its operation is based on the propagation of a cold plasma surface wave. This device can work (in argon for example) at pressures from 2 mTorr to 20 Torr with electron densities from 1010 cm-3 to 1013 cm-3, depending on plasma diameter and HF power. Typically, 80W of 500 MHz HF will produce a 25 mn diameter column of 1.8 m length. The plasma is quiescent (low electron density fluctuations), efficient (~ 100% absorbed power), and perfectly reproducible. It can be used as a substitute for a positive column, and some practical applications are foreseen in ion production, laser excitation, gas preionization and spectroscopic sources.
Open loop control of multiple drug effects in anesthesia (1995)

Current open-loop computer-controlled infusion pumps do not explicitly control the transient adverse side effects of intravenous drugs during anesthesia. We used optimal control principles to synthesize a single-input multiple-output controller that regulates concentrations at the site of desirable drug effect while penalizing excessive side-effect drug concentrations. The cost function incorporates model-based predictions of future effect-site concentrations, and the capability of the anesthesiologist to anticipate upcoming surgical events. The controller was evaluated and then compared with alternative control strategies through computer simulation of a physiologically based pharmacokinetic model for the intravenous drug alfentanil. Multiple-effect control offers an analytic approach to limit the overshoot in adverse side-effect concentrations at the consequence of increasing the time to achieve the desired drug effect.
Waveguide-based single and multiple nozzle plasma torches: the TIAGO concept (2001)

Various microwave-sustained, atmospheric-pressure plasma torches have been developed, investigated and applied over the last few decades. To avoid some of their shortcomings, we have designed a novel torch termed TIAGO (Torche à Injection Axiale sur Guide d'Ondes, in French). Its main advantages are simplicity, smooth impedance matching (low sensitivity to changes in operating conditions) and a short gas channel to prevent vapour condensation. Furthermore, it is possible to arrange TIAGOs in arrays to form a compact torch system which can be supplied, with equal distribution of power between plasma flames, from a single waveguide. This unique feature makes the new device particularly suitable when high gas throughputs or sequential processing are required. We describe the design, electrodynamic characteristics and experimental investigation of various torch arrangements based on the TIAGO principle, operated at 2.45 GHz with powers of a few hundred watts up to 2-3 kW per nozzle.
Domain-specific Interactions between the p185 and Epidermal Growth Factor Receptor Kinases Determine Differential Signaling Outcomes (1999)

We expressed the epidermal growth factor receptor (EGFR) along with mutant p185(neu) proteins containing the rat transmembrane point mutation. The work concerned the study of the contributions made by various p185(neu) subdomains to signaling induced by a heterodimeric ErbB complex. Co-expression of full-length EGFR and oncogenic p185(neu) receptors resulted in an increased EGF-induced phosphotyrosine content of p185(neu), increased cell proliferation to limiting concentrations of EGF, and increases in both EGF-induced MAPK and phosphatidylinositol 3-kinase (PI 3-kinase) activation. Intracellular domain-deleted p185(neu) receptors (T691stop neu) were able to associate with full-length EGFR, but induced antagonistic effects on EGF-dependent EGF receptor down-regulation, cell proliferation, and activation of MAPK and PI 3-kinase pathways. Ectodomain-deleted p185(neu) proteins (TDelta5) were unable to physically associate with EGFR, and extracellular domain-deleted p185(neu) forms failed to augment activation of MAPK and PI 3-kinase in response to EGF. Association of EGFR with a carboxyl-terminally truncated p185(neu) mutant (TAPstop) form did not increase transforming efficiency and phosphotyrosine content of the TAPstop species, and proliferation of EGFR.TAPstop-co-expressing cells in response to EGF was similar to cells containing EGFR only. Thus, neither cooperative nor inhibitory effects were observed in cell lines co-expressing either TDelta5 or TAPstop mutant proteins. Unlike the formation of potent homodimer assemblies composed of oncogenic p185(neu), the induction of signaling from p185(neu).EGFR heteroreceptor assemblies requires the ectodomain for ligand-dependent physical association and intracellular domain contacts for efficient intermolecular kinase activation.
Extending mobile computer battery life through energy-aware adaptation (2001)

Energy management has been a critical problem since the earliest days of mobile computing. The amount of work one can perform while mobile is fundamentally constrained by the limited energy supplied by one's battery. Although a large research investment in low-power circuit design and hardware power management has led to more energy-efficient systems, there is a growing realization that more is needed the higher levels of the system, the operating system and applications, must also contribute to energy conservation. This dissertation puts forth the claim that energy-aware adaptation, the dynamic balancing of application quality and energy conservation, is an essential part of a complete energy management strategy. Energy-aware applications identify possible tradeoffs between energy use and application quality, but defer decisions about which tradeoffs to make until runtime. The operating system uses additional information available during execution, such as resource supply and demand, to advise applications which tradeoffs are best. This dissertation first shows how one can measure the energy impact of the higher levels of the system. It describes the design and implementation of PowerScope, an energy profiling tool that maps energy consumption to specific code components. PowerScope helps developers increase the energy-efficiency of their software by focusing attention on those processes and procedures that are responsible for the bulk of energy use. PowerScope is used to perform a detailed study of energy-aware adaptation, focusing on two dimensions: reduction of data and computation quality, and relocation of execution to remote machines. The results of the study show that applications can significantly extend the battery lifetimes of the systems on which they execute by modifying their behavior. On some platforms, quality reduction and remote execution can decrease application energy usage by up to 94%.
Sector Resection With or Without Postoperative Radiotherapy for Stage I Breast Cancer: Five-Year Results of a Randomized Trial (1994)

The increase in recurrence rate observed over time suggests that surgical technique and patient selection should be improved. The benefits of reduced cost and patient inconvenience that would result from the elimination of postoperative radiotherapy must be carefully weighed against the disadvantages of local recurrence. Longer term follow-up must be done to estimate the risk of cancer recurrence in these women 10 and 15 years later, and methods must be developed to identify those women who have a higher risk of recurrence. Finally, economic analyses of this and similar trials are needed to give empirical underpinnings for optimal use of radiotherapy.
Surrogate endpoints in clinical trials: Definition and operational criteria (1989)

I discuss the idea of using surrogate endpoints in the context of clinical trials to compare two or more treatments or interventions in respect to some 'true' endpoint, typically a disease occurrence. In order that treatment comparison based on a surrogate response variable have a meaningful implication for the corresponding true endpoint treatment comparison, a rather restrictive criterion is proposed for use of the adjective 'surrogate'. Specifically, I propose that a surrogate for a true endpoint yield a valid test of the null hypothesis of no association between treatment and the true response. This criterion essentially requires the surrogate variable to 'capture' any relationship between the treatment and the true endpoint, a notion that can be operationalized by requiring the true endpoint rate at any follow-up time to be independent of treatment, given the preceding history of the surrogate variable. I then discuss this operational criterion in the examples of the accompanying papers and in the setting of trials aimed at the primary and secondary prevention of cancer.
Investigation of Coherent Optical Multiband DFT-S OFDM in Long Haul Transmission (2012)

Multiband discrete Fourier transform spread (DFT-S) is a promising technology to reduce peak-to-average power ratio and mitigate the fiber nonlinearity. We investigate DFT-S coherent optical orthogonal frequency division multiplexing (CO-OFDM) in terms of computational complexity and nonlinearity. With the nonlinearity improvement, 450-Gb/s two-band DFT-S CO-OFDM outperforms conventional CO-OFDM, and is successfully transmitted over a 9280-km fiber link.
Evolutionary‐based grouping of haplotypes in association analysis (2005)

Haplotypes incorporate more information about the underlying polymorphisms than do genotypes for individual SNPs, and are considered as a more informative format of data in association analysis. To model haplotypes requires high degrees of freedom, which could decrease power and limit a model's capacity to incorporate other complex effects, such as gene-gene interactions. Even within haplotype blocks, high degrees of freedom are still a concern unless one chooses to discard rare haplotypes. To increase the efficiency and power of haplotype analysis, we adapt the evolutionary concepts of cladistic analyses and propose a grouping algorithm to cluster rare haplotypes to the corresponding ancestral haplotypes. The algorithm determines the cluster bases by preserving common haplotypes using a criterion built on the Shannon information content. Each haplotype is then assigned to its appropriate clusters probabilistically according to the cladistic relationship. Through this algorithm, we perform association analysis based on groups of haplotypes. Simulation results indicate power increases for performing tests on the haplotype clusters when compared to tests using original haplotypes or the truncated haplotype distribution.
One target, different effects: a comparison of distinct therapeutic antibodies against the same targets (2011)

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.
Development of Externally Powered Lower Limb Orthosis with Bilateral-Servo Actuator (2005)

The externally powered orthosis is one of the necessary devices for rehabilitation of paraplegia patients and hemiplegia patients and spinal-cord-injury victims. However, the main problems of speed, noise, and weight and so on make the morale of the training lower. Then, we thought that there were problems in the actuator. To overcome these problems, we have developed the orthosis externally powered by bi-articular muscle mechanism with a bilateral-servo actuator. Our study suggests such a system as the physically disabled can train with the externally powered orthosis and ambulation device in smooth action.
Femoral intra‐arterial injection: a tool to deliver and assess recombinant AAV constructs in rodents whole hind limb (2005)

With the aim of simplifying recombinant-adeno-associated virus (rAAV) delivery in muscle, a new femoral intra-arterial technique was designed and tested in rodents (rats and mice). Two serotypes, several promoters and transgenes (reporter or therapeutic) were tested using this administration route. The new route is both easy to perform and efficient. Its usefulness as a tool to assess gene delivery constructs in the muscle was established in the context of recombinant AAV serotypes 1 and 2, and with the ubiquitous CMV and two muscle-specific (C5-12 and CK6) promoters. Both serum monitoring of a secreted protein (murine alkaline phosphatase: muSEAP) and slide staining were used to compare the different constructs. Significantly different patterns of expression in kinetics of expression (muSEAP) and homogeneity of fiber transduction (staining) were evidenced with the different promoters tested, and compared with intra-muscular expression patterns. Detailed studies of differential transduction in leg and thigh muscles showed equivalent efficacy, except in rectus femoris, and to a lesser extent in soleus. In light of these results and prior data, intra-arterially mediated gene transfer mechanism is discussed.
Clinical evaluation of a simple image cytometer for CD4 enumeration on HIV‐infected patients (2009)

Evaluation of the image cytometer for CD4 and CD8 enumeration demonstrated comparable results with FCM on a population of HIV-1-infected patients. The image cytometer is a good alternative method for point-of-care settings in resource-constrained countries.
A compact design for the Josephson mixer: The lumped element circuit (2015)

We present a compact and efficient design in terms of gain, bandwidth, and dynamical range for the Josephson mixer, the superconducting circuit performing three-wave mixing at microwave frequencies. In an all lumped-element based circuit with galvanically coupled ports, we demonstrate nondegenerate amplification for microwave signals over a bandwidth up to 50 MHz for a power gain of 20 dB. The quantum efficiency of the mixer is shown to be about 70%, and its saturation power reaches −112 dBm.
Urokinase-type plasminogen activator receptors associate with beta1 and beta3 integrins of fibrosarcoma cells: dependence on extracellular matrix components. (1997)

We have shown previously that the urokinase-type plasminogen activator receptor (uPAR) physically associates with beta2 integrins on human leukocyte membranes. We now report that uPAR associates with certain members of the beta1 and beta3 integrin families expressed by a nonhematopoietic fibrosarcoma cell line (HT1080) when adherent to certain extracellular matrix molecules. Flow cytometry studies indicated that HT1080 cells expressed uPAR and beta1 and beta3 integrins. Double staining immunofluorescence was used to label uPAR and beta1 and beta3 integrins. The staining patterns of uPAR and beta1 integrins were strikingly similar when attached to fibronectin, laminin, or vitronectin but not polylysine-coated substrates. Resonance energy transfer (RET) between uPAR and beta1 integrins was observed, especially at focal adhesion plaques; this indicates that these molecules are within about 7 nm of each other on these cell membranes. uPAR and beta3 integrin coclustering and RET were also observed on tumor cells adherent to vitronectin but not to fibronectin, laminin, or polylysine-coated surfaces. Because N-acetyl-D-glucosamine was found previously to inhibit beta2 integrin-uPAR association, we tested the effect of saccharides on the beta1-uPAR and beta3-uPAR colocalization and RET. Colocalization and RET between uPAR and beta1 or beta3 integrins were effectively inhibited by N-acetyl-D-glucosamine on extracellular matrix-coated surfaces. To better define which members of beta1 and beta3 integrin families associate with uPAR, we studied the association of several alpha subunits with uPAR on tumor cells. We found that: (a) alpha5 colocalizes with uPAR on cells attached to fibronectin-coated surfaces; (b) alpha5 and alpha(v) colocalize with uPAR on cells adherent to vitronectin; and (c) alpha3 and alpha6 associate with uPAR on cells attached to laminin. In further support of physical associations between integrins and uPAR on tumor cells, uPAR was found to coimmunoprecipitate with beta1 integrins in Brij-58 lysates of HT1080 cells (as detected by anti-uPAR Western blotting of material isolated from an anti-beta1 integrin immunoaffinity column). Thus, uPAR may laterally associate with integrins of tumor cells when attached to specific extracellular matrix elements to enable directional proteolysis for tumor cell migration and invasion.
Receptor-Mediated Delivery of CRISPR-Cas9 Endonuclease for Cell-Type-Specific Gene Editing (2018)

CRISPR-Cas RNA-guided endonucleases hold great promise for disrupting or correcting genomic sequences through site-specific DNA cleavage and repair. However, the lack of methods for cell- and tissue-selective delivery currently limits both research and clinical uses of these enzymes. We report the design and in vitro evaluation of S. pyogenes Cas9 proteins harboring asialoglycoprotein receptor ligands (ASGPrL). In particular, we demonstrate that the resulting ribonucleoproteins (Cas9-ASGPrL RNP) can be engineered to be preferentially internalized into cells expressing the corresponding receptor on their surface. Uptake of such fluorescently labeled proteins in liver-derived cell lines HEPG2 (ASGPr+) and SKHEP (control; diminished ASGPr) was studied by live cell imaging and demonstrates increased accumulation of Cas9-ASGPrL RNP in HEPG2 cells as a result of effective ASGPr-mediated endocytosis. When uptake occurred in the presence of a peptide with endosomolytic properties, we observed receptor-facilitated and cell-type specific gene editing that did not rely on electroporation or the use of transfection reagents. Overall, these in vitro results validate the receptor-mediated delivery of genome-editing enzymes as an approach for cell-selective gene editing and provide a framework for future potential applications to hepatoselective gene editing in vivo.