gebhart/patrepeval huggingface dataset:
521. Platelets Transfusion New Role as Brain Therapeutics for Acute Neuronopathic Gaucher Disease (2016)

There has no effective treatment for neuronopathic Gaucher Disease (nGD) due to the difficulty of therapeutics to cross the blood-brain-barrier. Platelets are blood elements that contain cytoplasmic secretory vesicles containing proteins involved in hemostasis, inflammation and angiogenesis. We have recently shown that platelets/megakaryocytes could serve as efficient and protective depots for lysosomal enzyme generation and distribution. In this study the potential therapeutic benefits of platelet transfusion in treating neuronopathic GD (nGD) was evaluated using a murine model of acute nGD (4L;C), which resembles types 2 and 3 Gaucher disease. Platelets containing significant amounts of wild type acid ß-glucosidase enzyme (GCase) were isolated from GFP mice and transfused weekly into 4L;C mice for four times beginning at 21 days of age, resulting in an average 10-13% of donor-derived GFP+ platelets in circulation with half-life of 52 hr. Importantly, moderate platelet transfusion led to significantly increase of life-span in 4L;C mice from 47 days to 55 days with reduction of splenomegaly. The accumulation of glycosylsphingosin was significantly reduced in spleen, liver and brain. Moreover, the abnormal walk patterns with splaying of hindlimbs exhibited in 4L;C mice were improved significantly in platelet-treated mice, indicating amelioration of motor neuron dysfunction and hindlimb paresis. The improvement of short-term memory deficit in treated 4L;C mice was evidenced in repeated open-field test. Immunohistochemistry analysis showed that the elevated brain CD68+ signals, a marker for activated microglia cells, were normalized in cerebellum folium and middle brain regions, and partially corrected in the cortex, cerebellum DCN, brainstem, thalamus and spinal cord of treated 4L;C mice, indicating the reduction of pro-inflammation by platelet transfusion. Notably, RIPK3-positive signals within Purkinje neurons in cerebellum of nGD mice were significantly reduced, suggesting therapeutic benefit of platelet transfusion on neuronal necroptosis. This study reveals an under-appreciated, unexpected role for platelets in treating CNS diseases. These results provide proof of concept that platelet transfusion can achieve CNS benefits with brain substrate reduction and improvement in neurological function, as well as reducing pro-inflammation and neuronal necroptosis. The findings will open a door for new clinical approaches with platelet transfusion in treating nGD and potentially other brain diseases.
Abstract 4272: Potent <i>in situ</i> cancer immunotherapy with synthetic human STING-activating cyclic dinucleotides (2015)

Abstract Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. Based on recent observations indicating that IFN-β expression was dependent upon activation of the host STING (Stimulator of Interferon Genes) pathway, we hypothesized that direct engagement of STING through intratumoral administration of specific agonists would result in effective anti-tumor therapy. To this end, we generated novel synthetic cyclic dinucleotide (CDN) derivatives with superior STING-activating and anti-tumor properties. The most potent molecule contains a 2′-5′ and 3′-5′ phosphate bridge that increases its affinity for STING at least 10-fold. Additionally, sulfur atoms at the non-bridging oxygens of the internucleotide phosphate bridge enable both superior STING binding affinity, as well as resistance to host cell phosphodiesterases. Importantly, the lead molecule activates PBMCs from a panel of human donors representing all known STING alleles, including homozygotes for the most refractory allele. Intratumoral injection of the lead CDN molecule induced profound regression of established B16 melanoma tumors, generated substantial systemic immune responses capable of rejecting distant metastases and provided long-lived immunologic memory. Cures in entire cohorts of mice bearing well-established 4T1 mammary and CT26 colon carcinoma models correlated with induction of cytokine-mediated innate and adaptive antigen-specific T cell immunity, both systemically and in the tumor microenvironment. Immune activation and anti-tumor efficacy was lost in mice encoding non-functional STING. In vivo activation of STING with the lead CDN administered by multiple routes demonstrated a high safety and tolerability margin in preclinical toxicology studies. In addition, pharmacokinetic analysis indicates that the lead CDN compound was rapidly cleared from systemic circulation, consistent with pulsatile STING activation and transient systemic cytokine and hematological changes. These results demonstrate that CDNs have high translation potential for treatment strategies to induce activation of the tumor microenvironment, leading to effective tumor-initiated T cell priming and anti-tumor immunity. Citation Format: Laura Hix Glickman, David B. Kanne, Kelsey E. Gauthier, George E. Katibah, Justin J. Leong, Ken Metchette, Thomas W. Dubensky, Sarah M. McWhirter. Potent in situ cancer immunotherapy with synthetic human STING-activating cyclic dinucleotides. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4272. doi:10.1158/1538-7445.AM2015-4272
Grafting byin situ coupling of epoxy groups of a living copolymer with an anionic living polymer (1999)

A tetrahydrofuran (THF) solution of the living random copolymer of methyl methacrylate (MMA) and glycidyl methacrylate (GMA) was prepared by the living anionic copolymerization of the two monomers, using 1,1-diphenylhexyllithium (DPHLi) as initiator, in the presence of LiCl ([LiCl]/[DPHLi]0 = 3), at −50°C. The copolymer thus obtained has a controlled composition and molecular weight and a narrow molecular weight distribution. By introduction of an anionic living polystyrene (poly(St)) or anionic living polyisoprene (poly(Is)) solution into the above system at −30°C, a coupling reaction took place and a graft copolymer with a polar backbone and nonpolar side chains was produced. The solvent used in the preparation of the living poly(St) or poly(Is) affects the coupling reaction. When benzene was the solvent, a graft copolymer of high purity, controlled graft number and molecular weight, and narrow molecular weight distribution (Mw/Mn = 1.11–1.21) was obtained. In the coupling reaction, the living poly(St) reacted only with the epoxy groups and not with the carbonyls of the backbone polymer. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 105–112, 1999
Fiber-Optic Sources of Quantum Entanglement (2002)

We present a fiber-based source of polarization-entangled photon pairs that is well suited for quantum communication applications in the 1.5$μ$m band of standard telecommunication fiber. Quantum-correlated signal and idler photon pairs are produced when a nonlinear-fiber Sagnac interferometer is pumped in the anomalous-dispersion region of the fiber. Recently, we have demonstrated nonclassical properties of such photon pairs by using Geiger-mode InGaAs/InP avalanche photodiodes. Polarization entanglement in the photon pairs can be created by pumping the Sagnac interferometer with two orthogonally polarized pulses. In this case the parametrically scattered signal-idler photons yield biphoton interference with $>$90% visibility in coincidence detection, while no interference is observed in direct detection of either the signal or the idler photons.
Controlled Generation of Double Emulsions in Air (2013)

This Letter describes the controlled generation of double emulsions in the gas phase, which was carried out using an integrated emitter in a poly(dimethylsiloxane) (PDMS) microfluidic chip. The integrated emitter was formed using a molding approach, in which metal wires with desirable diameters were used as emitter molds. The generation of double emulsions in air was achieved with electrohydrodynamics actuation, which offers controllable force exerting on the double emulsions. We developed this capability for future integration of droplet microfluidics with mass spectrometry (MS), where each aqueous droplet in the microchannel is introduced into the gas phase as a double emulsion for subsequent ionization and MS analysis.
Performance evaluation of a tri-axial accelerometry-based respiration monitoring for ambient assisted living (2009)

Ambient Assisted Living (AAL) technology is often proposed as a way to tackle the increasing cost of healthcare caused by population aging. However, the sensing technology for continuous respiratory monitoring at home is lacking. Known approaches of respiratory monitoring are based on measuring either respiratory effect, e.g. tracheal sound recording by a bio-acoustic sensor, or respiratory effort, e.g. abdomen movement measurement by a tri-axial accelerometer. This paper proposes a home respiration monitoring system using a tri-axial accelerometer. Three different methods to extract a single respiratory signal from the tri-axial data are proposed and analyzed. The performance of the methods is evaluated for various possible respiration conditions, defined by the sensor orientation and respiration-induced abdomen movement. The method based on Principal Component Analysis (PCA) performs better than selecting the best axis. The analytical approach called Full Angle shows worse results than the best axis when the gravity vector is close to one of the sensor's axes (<15 degrees). Hybrid-PCA, which is a combination of both methods, performs comparable to PCA. The system is evaluated using simulated data from the most common postures, such as lying and sitting, as well as real data collected from five subjects. The results show that the system can successfully reconstruct the respiration-induced movement, which is necessary to determine the respiratory rate accurately.
Synthesis of Tetrazole Oxathiolane Nucleoside Analogues and Their Evaluation as HIV-1 Antiviral Agents (1992)

Abstract The synthesis of The synthesis of 2-hydroxymethyl-5-[N2-(5′-carboxamido tetrazolyl)]-1,3-oxathiolane (6a and 6b) and 2-hydroxymethyl-5-[N2-(5′-aminotetrazolyl)]-1,3-oxathiolane (7a and 7b) is described. It involved the preparation of suitable 1,3-oxathiolane precursors via cyclocondensation between benzoyloxyacetaldehyde and 2-mercaptoacetaldehyde di-[2-methoxyethyl] acetal, followed by condensation of adequately substituted tetrazoles using trimethylsilyltriflate or titanium tetrachloride as acid catalysts. In a preliminary in vitro study these new tetrazole oxathiolane nucleoside analogues were found inactive against HIV-1 retrovirus.
Gabriella: An Online System for Real-Time Activity Detection in\n Untrimmed Security Videos (2020)

Activity detection in security videos is a difficult problem due to multiple\nfactors such as large field of view, presence of multiple activities, varying\nscales and viewpoints, and its untrimmed nature. The existing research in\nactivity detection is mainly focused on datasets, such as UCF-101, JHMDB,\nTHUMOS, and AVA, which partially address these issues. The requirement of\nprocessing the security videos in real-time makes this even more challenging.\nIn this work we propose Gabriella, a real-time online system to perform\nactivity detection on untrimmed security videos. The proposed method consists\nof three stages: tubelet extraction, activity classification, and online\ntubelet merging. For tubelet extraction, we propose a localization network\nwhich takes a video clip as input and spatio-temporally detects potential\nforeground regions at multiple scales to generate action tubelets. We propose a\nnovel Patch-Dice loss to handle large variations in actor size. Our online\nprocessing of videos at a clip level drastically reduces the computation time\nin detecting activities. The detected tubelets are assigned activity class\nscores by the classification network and merged together using our proposed\nTubelet-Merge Action-Split (TMAS) algorithm to form the final action\ndetections. The TMAS algorithm efficiently connects the tubelets in an online\nfashion to generate action detections which are robust against varying length\nactivities. We perform our experiments on the VIRAT and MEVA (Multiview\nExtended Video with Activities) datasets and demonstrate the effectiveness of\nthe proposed approach in terms of speed (~100 fps) and performance with\nstate-of-the-art results. The code and models will be made publicly available.\n
Direct Imprinting of Porous Substrates (2011)

We present “direct imprinting of porous substrates” (DIPS) as a strategy for nanoscaled (<100nm) patterning of porous nanomaterials. DIPS is further investigated as a low-cost, high-throughput technique for fabricating optical structures with enhanced light-matter interaction.
Photonuclear Production of <sup>67</sup> Cu From Gallium (2023)

Copper-67 is a radioisotope of interest for medical imaging and therapy as well as for under- standing stellar and interstellar evolution pertaining to the formation of proton-rich nuclei. Since <sup>67</sup>Cu decays 100% to <sup>67</sup>Zinc, understanding this reaction can shed light on the abundance of this and other p-nuclei elements in the universe. Here, the photonuclear production of <sup>67</sup>Cu from <sup>71</sup>Ga and natural gallium is examined as an alternative to its photoproduction from zinc. Two research and development production runs were performed at Thomas Jefferson National Accelerator Facility using an electron linac. During the first run, an 805-W, 30.9-MeV beam was used to irradiate a 1-mm tungsten radiator to create a bremsstrahlung flux. The resulting gamma photons irradiated 50.9 g of natural gallium encased in a graphite crucible for 24.2 h; 7.02 Bq/W∙s∙kg of <sup>67</sup>Cu activity was produced. During the second run, a 4380-W, 31.5-MeV beam was used for 12.0 h on the same target containing 60 g of natural gallium; 6.41 Bq/W∙s∙kg of <sup>67</sup>Cu activity was produced. Because of the difficulties in spectroscopically differentiating <sup>67</sup>Cu from <sup>67</sup>Ga, prior to each run, an isotopically pure <sup>71</sup>Ga disk was irradiated using a 100-W beam for 1 h, at the same respective energies. Finally, these baseline irradiations allowed for separation of <sup>67</sup>Cu from <sup>67</sup>Ga in the spectroscopic measurements of the natural gallium targets.
Abstract 2848: IgE-mediated immune activation targeting the prostate specific antigen: a potential prostate cancer therapy. (2013)

Abstract Prostate cancer (PCa) is the second leading cause of cancer deaths among men in the United States. The prostate-specific antigen (PSA), often found at high levels in the serum of PCa patients, has been used as a marker for PCa detection and as a target of immunotherapy. The murine IgG1 monoclonal antibody AR47.47, specific for human PSA, has been shown to enhance antigen presentation by human dendritic cells and induce both CD4 and CD8 T-cell activation when complexed with PSA. In this study, we explored the properties of a novel mouse/human chimeric anti-PSA IgE containing the variable regions of AR47.47 as a potential therapy for PCa. Our goal is to take advantage of the unique properties of the IgE molecule in order to trigger immune activation against PCa. The properly assembled and secreted anti-PSA IgE binds the antigen and the Fc epsilon RI (FcεRI) as demonstrated by ELISA and flow cytometry, respectively. This novel IgE antibody is capable of triggering effector cell degranulation in vitro as determined by the release of β-hexosaminidase from rat basophil leukemic effector cells that express human FcεRI (RBL SX-38). Furthermore, the IgE triggered degranulation in vivo in human FcεRIα transgenic mice using the passive cutaneous anaphylaxis assay. Degranulation was only observed when the IgE was artificially cross-linked, but not in the presence of the natural soluble antigen, suggesting that such an interaction will not trigger systemic anaphylaxis in patients. Importantly, when incubated in vitro with human dendritic cells the anti-PSA IgE complexed with the antigen (PSA) triggered autologous CD4 and CD8 T-cell activation, suggesting enhancement of antigen presentation. Immune activation was also observed in vivo where a prophylactic vaccination with the anti-PSA IgE complexed to PSA significantly prolonged the survival of human FcεRIα transgenic mice challenged with PSA-expressing tumors, under conditions in which its chimeric mouse/human anti-PSA IgG1 counterpart failed to confer protection. Our results provide initial proof-of principle that the anti-PSA IgE can stimulate immune activation against tumor cells expressing PSA, and further studies on the anti-tumor activity of this antibody are warranted. These studies belong to the new field of AllergoOncology that aims to reveal the function of IgE-mediated immune responses against cancer and develop novel IgE-based cancer therapies. Citation Format: Tracy R. Daniels-Wells, Gustavo Helguera, Richard K. Leuchter, Rafaela Quintero, Maggie Kozman, Jose A. Rodríguez, Elizabeth Ortiz-Sánchez, Otoniel Martínez-Maza, Birgit C. Schultes, Christopher F. Nicodemus, Manuel L. Penichet. IgE-mediated immune activation targeting the prostate specific antigen: a potential prostate cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2848. doi:10.1158/1538-7445.AM2013-2848
An efficient load-balancing algorithm for image processing applications on multicore processors (2008)

The significance of load-balancing is rising with the increasing number of processing cores per chip. A fast load-balancer is sought to exploit fine grain parallelism possible with multicore processors. This paper focuses on load-balancing image processing applications where the amount of processing varies per pixel; such application domain includes high dynamic range imaging and fractal related applications. This paper formulates load-balancing, for such applications, as a curve fitting problem for statistically sampled work across the image. Such formulation allows for analytically determining an optimal load-balance partitioning, resulting in accurate, low-overhead load-balancing. Experiments using the proposed algorithm shows a remarkable performance of achieving around 90% of 'perfect' image partitioning for a complex fractal application.
Analytical electron microscopy of grain boundaries in Al-Cu metallizations (1992)

Al with additions of Cu is commonly used as the conductor metallizations for integrated circuits, the Cu being added since it improves resistance to electromigration failure. As linewidths decrease to submicrometer dimensions, the current density carried by the interconnect increases dramatically and the probability of electromigration failure increases. To increase the robustness of the interconnect lines to this failure mode, an understanding of the mechanism by which Cu improves resistance to electromigration is needed. A number of theories have been proposed to account for role of Cu on electromigration behavior and many of the theories are dependent of the elemental Cu distribution in the interconnect line. However, there is an incomplete understanding of the distribution of Cu within the Al interconnect as a function of thermal history. In order to understand the role of Cu in reducing electromigration failures better, it is important to characterize the Cu distribution within the microstructure of the Al-Cu metallization.
Anticancer and Cytotoxic Properties of Mannich Bases (1997)

This review outlines the chemistry and anticancer and cytotoxic properties of certain Mannich bases. It is divided into four parts. The first section summarizes briefly various investigations undertaken by other researchers of the chemical and pharmacological properties of a number of Mannich bases against neoplasms. The remaining portions of this review are summaries of work undertaken in this laboratory. The second part presents the following aspects of the anticancer properties of various Mannich bases namely differences in antileukemic activity between certain conjugated styryl ketones and the related Mannich bases, intramolecular cyclization of various acyclic Mannich bases and the effect on anticancer activity of such a process, prodrug approaches with a view to obtaining preferential toxicity to cancerous rather than normal cells and finally the effect on antineoplastic properties of introducing a second basic centre into these compounds. The third section summarizes the promising in vitro activities of different acyclic Mannich bases against the WiDr human colon cancer cells and the preparation of a group of Mannich bases which are effective against certain drug resistant malignant cells. The evidence for and evaluations of a theory proposed by one of the authors called sequential cytotoxicity is presented followed by a description of the very high cytotoxicity of some 4-piperidones; a group of compounds which may be regarded as cyclic Mannich bases. Finally, some biochemical properties of certain of these compounds are outlined especially with reference to their causing inhibition of respiration in mitochondria, particularly in those organelles obtained from neoplastic tissue.
Attainable Burnup in a LIFE Engine Loaded with Depleted Uranium (2009)

The Laser Inertial Fusion-based Energy (LIFE) system uses a laser-based fusion source for electricity production. The (D,T) reaction, beside a pure fusion system, allows the option to drive a sub-critical fission blanket in order to increase the total energy gain. In a typical fusion-fission LIFE engine the fission blanket is a spherical shell around the fusion source, preceded by a beryllium shell for neutron multiplications by means of (n,2n) reactions. The fuel is in the form of TRISO particles dispersed in carbon pebbles, cooled by flibe. The optimal design features 80 cm thick blanket, 16 cm multiplier, and 20% TRISO packing factor. A blanket loaded with depleted uranium and depleted in a single batch with continuous mixing can achieve burnup as high as {approx}85% FIMA while generating 2,000 MW of total thermal power and producing enough tritium to be used for fusion. A multi-segment blanket with a central promotion shuffling scheme enhances burnup to {approx}90% FIMA, whereas a blanket that is operated with continuous refueling achieves only 82% FIMA under the same constraints of thermal power and tritium self-sufficiency. Both, multi-segment and continuous refueling eliminate the need for a fissile breeding phase.
ChemInform Abstract: Introduction of Fluorine and Fluorine‐Containing Functional Groups (2013)

Abstract Review: < 550 refs.
Sampling Method for Fast Training of Support Vector Data Description (2018)

Support Vector Data Description (SVDD) is a popular outlier detection technique, which constructs a flexible description of the input data. SVDD computation time is high for large training datasets, which limits its use in big-data process monitoring applications. We propose a new iterative, sampling-based method for SVDD training. The method incrementally learns the training data description at each iteration by computing SVDD on an independent random sample selected with replacement from the training data set. The experimental results indicate that the proposed method is extremely fast and provides a good quality data description.
Practical estimate of gradient nonlinearity for implementation of apparent diffusion coefficient bias correction (2013)

Empiric scalar adjustment of an independent gradient nonlinearity model adequately described DWI bias for a clinical scanner. Observed efficiency of implemented ADC bias correction quantitatively agreed with previous theoretical predictions and numerical simulations. The described procedure provides an independent benchmark for nonlinearity bias correction of clinical MRI scanners.