gebhart/patrepeval huggingface dataset:
Oncolytic virotherapy with intratumoral injection of vaccinia virus TG6002 and 5-fluorocytosine administration in dogs with malignant tumors (2023)

TG6002 is an oncolytic vaccinia virus expressing FCU1 protein, which converts 5-fluorocytosine into 5-fluorouracil. The study objectives were to assess tolerance, viral replication, 5-fluorouracil synthesis, and tumor microenvironment modifications to treatment in dogs with spontaneous malignant tumors. Thirteen dogs received one to three weekly intratumoral injections of TG6002 and 5-fluorocytosine. The viral genome was assessed in blood and tumor biopsies by qPCR. 5-Fluorouracil concentrations were measured in serum and tumor biopsies by liquid chromatography or high-resolution mass spectrometry. Histological and immunohistochemical analyses were performed. The viral genome was detected in blood (7/13) and tumor biopsies (4/11). Viral replication was suspected in 6/13 dogs. The median intratumoral concentration of 5-fluorouracil was 314 pg/mg. 5-Fluorouracil was not detected in the blood. An increase in necrosis (6/9) and a downregulation of intratumoral regulatory T lymphocytes (6/6) were observed. Viral replication, 5-fluorouracil synthesis, and tumor microenvironment changes were more frequently observed with higher TG6002 doses. This study confirmed the replicative properties, targeted chemotherapy synthesis, and reversion of the immunosuppressive tumor microenvironment in dogs with spontaneous malignant tumors treated with TG6002 and 5-fluorocytosine.
Protecting the Router Control Plane (2011)

This memo provides a method for protecting a router's control plane from undesired or malicious traffic. In this approach, all legitimate router control plane traffic is identified. Once legitimate traffic has been identified, a filter is deployed in the router's forwarding plane. That filter prevents traffic not specifically identified as legitimate from reaching the router's control plane, or rate-limits such traffic to an acceptable level.
Fast direct solvers for Poisson equation on 2D polar and spherical geometries (2001)

Abstract A simple and efficient class of FFT‐based fast direct solvers for Poisson equation on 2D polar and spherical geometries is presented. These solvers rely on the truncated Fourier series expansion, where the differential equations of the Fourier coefficients are solved by the second‐ and fourth‐order finite difference discretizations. Using a grid by shifting half mesh away from the origin/poles, and incorporating with the symmetry constraint of Fourier coefficients, the coordinate singularities can be easily handled without pole condition. By manipulating the radial mesh width, three different boundary conditions for polar geometry including Dirichlet, Neumann, and Robin conditions can be treated equally well. The new method only needs O ( MN log 2 N ) arithmetic operations for M × N grid points. © 2002 John Wiley &amp; Sons, Inc. Numer Methods Partial Differential Eq 18: 56–68, 2002
α-1-C-Butyl-1,4-dideoxy-1,4-imino-l-arabinitol as a Second-Generation Iminosugar-Based Oral α-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia (2012)

We report on the synthesis and the biological evaluation of a series of α-1-C-alkylated 1,4-dideoxy-1,4-imino-l-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. α-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 μM, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of α-1-C-butyl-LAB and miglitol are clearly different. Furthermore, α-1-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. α-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.
Production of Genetically Engineered Cells Releasing Neurotrophic Factors (2003)

The technique of neuronal transplantation provides a powerful tool to deliver many pharmacologically active agents into the brain to address some fundamental questions regarding the basic principles of brain function. For example, grafting of embryonic tissues or cells into the central nervous system (CNS) has been used to study neuronal development (McConnell, 1985; Sotelo and Alvarado-Mallart, 1986; O’Leary and Stanfield, 1989), the factors necessary for the survival of axotomized neurons, and axon elongation from damaged neuronal populations (Blakemore and Franklin, 1991; Dunnett, 1991; Lindvall, 1991). In addition, foreign tissues and cells have been used for implantation in the CNS to replace the lost functions of neuronal populations in the damaged or diseased brain. An alternative approach to this application has focused on the genetic modifications of cells in vitro to produce specific products (e.g., growth factors) before their implantation into the brain (Gage et al., 1987,1991). In this strategy, defined populations of cells can be genetically modified to express the gene of interest, and the implantation of these cells can yield a graft consisting of phenotypically homogeneous cells. The success of this approach depends in large part on achieving efficient gene transfer and stable long-term gene expression in recipient cells. A number of efficient methods and vector systems have been described for gene transfer in immortalized and primary cells including postmitotic neurons. Although these methods have been used primarily to express reporter genes like β-galactosidase (β-gal), they are general methods that can be used to express other genes, such as growth factors. Nerve growth factor (NGF) is the only growth factor that has been expressed in cells and then implanted into the brain (Rosenberg et al., 1988; Stromberg et al., 1990; Kawaja and Gage, 1992a). However, the discovery of other growth factors and establishment of their roles and functions will facilitate their use in gene transfer.
Glycosphingolipid levels and glucocerebrosidase activity are altered in normal aging of the mouse brain (2018)

Aging is the predominant risk factor for both genetic and sporadic Parkinson's disease (PD). The majority of PD cases are nonfamilial, and the connection between aging and PD-associated genes is not well understood. Haploinsufficiency of the GBA gene, leading to a reduction in glucocerebrosidase (GCase) activity, is one of the most common genetic risk factors for PD. Furthermore, GCase activity is also reduced in brain regions of sporadic PD patients, with a corresponding accumulation of its glycosphingolipid (GSL) substrates. Recent findings in PD patients and aging control cases, and in human PD patient induced pluripotent stem cell neurons, have shown an age-dependent reduction in GCase activity and an elevation of some GSLs. We therefore asked whether aging-induced changes to both lysosomal and nonlysosomal GCase activity and GSL homeostasis in the brain could also be reflected in other nonhuman mammalian systems. Increases in brain polyubiquitin and the lysosomal-associated membrane protein, LAMP2A, were found in 24-month-old wild-type mice compared to 1.5-month-old mice. A lipidomic analysis was performed on brains of wild-type mice of different strains between 1.5 and 24 months of age. Aging created GSL changes that are reminiscent of sporadic PD. Levels of glucosylceramide, glucosylsphingosine, lactosylceramide, and GM1a were elevated in the brain of aged mice, and levels of complex gangliosides, GD1a, GD1b, and GT1b, were reduced with age. Parallel biochemical analyses revealed a change in lipid metabolism probably mediated by lysosomal hydrolases, with reduced GCase and increased neuraminidase activity. Based on these data, we hypothesize that perturbation of GSL metabolism in the aging brain may precede or may be part of abnormal protein handling and may accelerate PD pathophysiological processes in vulnerable neurons in PD and other age-related neurodegenerative disorders.
Supplementary Figures 1-4 from A Novel ALK Secondary Mutation and EGFR Signaling Cause Resistance to ALK Kinase Inhibitors (2023)

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A microrotary motor powered by bacteria (2006)

Biological molecular motors have a number of unique advantages over artificial motors, including efficient conversion of chemical energy into mechanical work and the potential for self-assembly into larger structures, as is seen in muscle sarcomeres and bacterial and eukaryotic flagella. The development of an appropriate interface between such biological materials and synthetic devices should enable us to realize useful hybrid micromachines. Here we describe a microrotary motor composed of a 20-mum-diameter silicon dioxide rotor driven on a silicon track by the gliding bacterium Mycoplasma mobile. This motor is fueled by glucose and inherits some of the properties normally attributed to living systems.
Pulling Mitigation in Wireless Transmitters (2014)

A new architecture to mitigate the unwanted pulling effect of a transmitter VCO pulled by its own transmitted signal or by other on-chip locked oscillators is presented. The proposed auto-calibration technique can run online without disturbing the transmitter functionality, and with no significant overhead on power consumption and area. When a 16QAM signal is transmitted and the TX-VCO is heavily pulled, the calibration improves the modulation mask by over 15 dB and lowers the transmitted EVM from 11% to 2.4%. Furthermore, the presented calibration technique suppresses unwanted sidebands caused by a mutual pulling between the TX-VCO and another nearby oscillator by more than 20 dB, where center frequencies of the two 4 GHz oscillators are spaced by only 3 MHz.
Weldability and microstructural characterization of Al-Li alloys (1989)

An investigation was carried out to determine the weldability, properties and microstructural characteristics of aluminum-lithium Alloys 2090 and 2091. Electron beam welds were made on 12.5-mm-thick plates to study the effect of welding conditions on the weldability and microstructure. The results indicate that these alloys are susceptible to fusion zone cracking. Following welding, a loss of hardness was observed in the fusion zone and the heat affected zone of Alloy 2090. After postweld aging the fusion zone hardness was partially restored and the heat-affected zone hardness was completely restored. Microhardness measurements did not reveal any such loss in hardness in the heat-affected zone of Alloy 2091. The result of the hot ductility tests indicate that these alloys are not susceptible to heat-affected zone cracking. 9 refs., 10 figs.
The Comparison of In Vitro and In Vivo Anti-Host Responses as a Predictor of T Cell Reactivity after Allogeneic-BMT as Determined by TCR Vb Spectratype Analysis. (2006)

Abstract Immunotherapeutic strategies have gained recognition as viable alternatives to more conventional therapeutic modalities for the treatment of cancer. In this regard, adoptive T cell therapy through allogeneic blood and marrow transplantation (BMT) has offered the first evidence to demonstrate that anti-tumor effects could be achieved against hematological malignancies. However, complications which include graft failure, opportunistic infections, leukemic relapse and graft-versus-host disease (GVHD) underscore the importance for the development of more targeted strategies in order to promote the successful implementation of allogeneic-BMT as a long term curative approach. It is well understood that mature donor T cells present in the donor inoculum must be an integral part of any such strategy as they play a pivotal role in all of the above mentioned complications. The incidence of the first three complications is diminished by the presence of mature donor T cells while, unfortunately, the transplantation of mature alloreactive donor T cells also directly induces the latter complication of acute GVHD, which can be directed against either HLA or minor histocompatibility antigen (miHA) disparities. Efforts to pan deplete donor marrow inoculum of T cells have been successful in minimizing the development of disease but have been associated with increased leukemic relapse. Thus, one approach to solve this problem would be to identify and then selectively deplete alloreactive donor T cells while allowing the residual T cells to provide protection against infection and to mediate a leukemia-specific GVL response. We hypothesized that an in vitro culture system using a one-way mixed lymphocyte reaction generated between a potential allogeneic BMT donor and their respective recipient could give rise to many of the alloreactive T cell responses that would be predictive of those that would be generated in vivo, following BMT. We proceeded to test the predictive value of the in vitro culture system through the use of TCR CDR3 Vβ spectratype analysis in the clinical BMT setting. To this end we compared, by spectratype analysis, the in vitro and post-transplant in vivo responses of nine donor patient pairs. The results indicated a high association of overlapping Vβ CDR3-size skewing as defined by the reactive Vβ families in the patient post-transplant also found to be reactive in the in vitro culture system (range of overlap 50–100%, median 72.5%). Thus, in vitro spectratyping analysis may be useful in guiding the manipulation of the donor T cell inoculum in order to provide improved BMT outcomes.
Bat-inspired dynamic features and factors that modulate their impact on speech recognition (2018)

One of the most serious remaining challenges in speech recognition is dealing with corruption of speech signal by other nuisance speech ("babble"). A promising approach to solving the problem of separating the signal of interest from the detractors is to inject direction dependent signatures into all signals received, which has been realized by bat-inspired biomimetic pinna—dynamic periphery. Changing the shape of a biomimetic pinna during the recordings introduces substantial time-variant signatures into speech signals. To investigate the utility of these signatures, we have used bioinspired signal representations (cochleagram and spikegram) as input for speech classifiers based on Gaussian mixture models (GMM) and hidden Markov models (HMM). The speech samples used were obtained from open source databases: spoken digits and alphabets from Carnegie Mellon University were mixed with babble or noise samples from Columbia University. Since the time-variant signatures were found to depend strongly on the direction of the sound source, we attempted to include datasets from different directions for training and testing to feed into the classifiers. The results indicate that dynamic periphery can substantially improve recognition and that these effects depend on the signal representation as well as the angular composition of the training dataset.
Intraoral JP4-039 to ameliorate irradiation-induced mucositis in tumor-bearing Fanconi anemia (FA) mouse model. (2014)

2571 Background: The DNA repair defect in Fanconi anemia (FA) patients makes radiotherapy of head and neck cancers a challenge due to mucositis as a dose limiting toxicity. We tested intraoral delivery of mitochondrial-targeted antioxidant, JP4-039, in a novel F15 emulsion, to reduce mucositis in fractionated irradiated FA mice with orthotopic tumors. Methods: Fancd2+/+, Fancd2+/-, and Fancd2-/-mice from C57BL/6J background with palpable tumors, measureable by calipers, were irradiated to single 28 Gy or 8 Gy x 4 daily fractions to the oral cavity. Subgroups of mice (N=4/group) received intraoral JP4-039/F15 (100 ul containing 4 mg/ml of drug) 10 minutes prior to irradiation, F15 alone or irradiation alone. Tumor size was measured daily. Five days after the last radiation dose, mice were sacrificed, and tumors and tongue tissue removed for histopathology. Statistical analysis was performed using Students t-test, with a p-value < 0.05 considered significant. Results: Intraoral JP4-039/F15 prior to irradiation significantly decreased oral cavity ulceration (p < 0.001). Following 8 Gy x 4, F15-JP4-039 treated Fancd2-/- knockout mice had 47.8 ± 11.1% of the tongue ulcerated compared to 81.7 ± 11.6% ulceration in untreated mice (p < 0.001). Results in JP4-039/F15 treated irradiated heterozygotes and wild-type Fancd2+/+ mice (34.1 ± 21.2 or 16.9 ± 12.6% ulceration, respectively) were also improved compared to untreated irradiated mice (88.3 ± 8.0 or 76.3 ± 17.2% ulceration, respectively) (p < 0.001 for all groups). F15 alone did not reduce ulceration. JP4-039/F15 treated FA mice had increased ulceration compared to Fancd2+/+ mice (47.8 ± 11.1% and 16.9 ± 12.6% respectively, p < 0.0001). Both single fraction and fractionated radiation treatment controlled tumors at 5 days in Fancd2+/+, Fancd2+/-, and Fancd2-/- mice (0.4 ± 0.3, 0.05 ± 0.05, or 0.1 ± 0.1 mm3, respectively) compared to nonirradiated controls (2.1 ± 0.4, 1.9 ± 0.5, or 3.1 ± 0.1 mm3, respectively, p < 0.027). Tumor size was comparably reduced in all irradiated groups. Conclusions: Intra oral JP4-039 protects normal tissue in irradiated FA mice without associated tumor protection.
Polyketomycin, a New Antibiotic from Streptomyces sp. MK277-AF1. I. Taxonomy, Production, Isolation, Physico-chemical Properties and Biological Activities. (1998)

A new antibiotic designated polyketomycin was isolated from the culture broth of Streptomyces sp. MK277-AF1. It was purified by ethyl acetate extraction, Sephadex LH-20 column chromatography and centrifugal partition chromatography (CPC). It inhibited growth of Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). Its MICs were less than 0.2 microgram/ml. Polyketomycin exhibited cytotoxic activity against nine tumor cell lines at concentrations of 0.9-5.2 micrograms/ml.
An Electron Paramagnetic Resonance Study of Defects in Interlayer Dielectrics (2011)

The electronic properties of thin film low-κ interlayer dielectric (ILD) and etch stop layers (ESL) are important issues in present day ULSI development (1-6). Low-κ ILD and ESLs with dielectric constants significantly less then those of SiO2 and SiN are utilized to reduce capacitance induced RC delays in ULSI circuits. Leakage currents, time dependent dielectric breakdown (TDDM) and stress induced leakage currents (SILC) are critical problems that are not yet well understood in ILD. A topic of current interest is ultraviolet light (UV curing) of low-k materials (5,6). We have made electron spin resonance (ESR) and current density versus voltage measurements on a moderately extensive set of dielectric/silicon structures involving materials of importance to low-k interconnect systems. Most of the dielectrics studied involve various compo-sitions of SiOC:H. In addition we have also made measurements on other dielectrics including SiO2, SiCN:H and SiN:H.
Planar silicon nitride mid-infrared devices (2013)

Integrated mid-infrared devices including (i) straight/bent waveguides and (ii) directional couplers are demonstrated on silicon nitride (SiN) thin films prepared by optimized low-pressure chemical vapor deposition. The deposited SiN film has a broad spectral transparency from visible up to a wavelength of λ = 8.5 μm (as seen from Fourier transform infrared spectroscopy). Our SiN waveguide shows a dominant fundamental mode with an optical loss of 2.1 dB/cm at λ = 3.7 μm. In addition, we demonstrate an efficient SiN directional coupler between λ = 3.55 μm to λ = 3.75 μm where an 8 dB extinction ratio is achieved within each channel upon wavelength scanning. With the inherent advantage of complementary metal–oxide–semiconductor compatibility, our SiN platform paves the way to create sophisticated photonic circuits that are desired for mid-infrared nonlinear light generation and chip-scale biochemical sensors.
Learning for autonomous navigation (2005)

Autonomous off-road navigation of robotic ground vehicles has important applications on Earth and in space exploration. Progress in this domain has been retarded by the limited lookahead range of 3-D sensors and by the difficulty of preprogramming systems to understand the traversability of the wide variety of terrain they can encounter. Enabling robots to learn from experience may alleviate both of these problems. We define two paradigms for this, learning from 3-D geometry and learning from proprioception, and describe initial instantiations of them we have developed under DARPA and NASA programs. Field test results show promise for learning traversability of vegetated terrain, learning to extend the lookahead range of the vision system, and learning how slip varies with slope. 1.
Long-term evaluation of adolescents treated operatively for spondylolisthesis. A comparison of in situ arthrodesis only with in situ arthrodesis and reduction followed by immobilization in a cast. (1992)

The medical records and radiographs of forty-two adolescents (twenty-three male and nineteen female) who had had a posterolateral spinal arthrodesis for spondylolisthesis between 1950 and 1986 were reviewed to assess the long-term outcome of this form of treatment. The average age of the patients at the time of the operation was fourteen years (range, seven years and nine months to seventeen years and eleven months). The duration of the clinical and radiographic follow-up ranged from two years to twenty-seven years and seven months. All patients had an in situ arthrodesis of the involved vertebrae. Eighteen patients had no additional intervention, and twenty-four patients had reduction and application of a cast. Use of the cast led to a decrease in sagittal translation of more than 5 per cent in eighteen patients and a decrease in lumbosacral kyphosis (the slip angle) of more than 5 degrees in fourteen patients. Of the patients who did not have a cast, eight had an increase in sagittal translation of more than 5 per cent and ten had an increase in lumbosacral kyphosis of more than 5 degrees. There were no neurological problems at the time of the initial operation or after the reduction maneuver. At the most recent clinical follow-up examination, thirty-eight patients had no complaints of low-back pain or any restriction of work-related or recreational activities. Persistent low-back pain and pain in the lower extremities limited the activities of the remaining four patients, two of whom had another operation to alleviate these symptoms.
Recent Advances in Adaptive Sampling and Reconstruction for Monte Carlo Rendering (2015)

Abstract Monte Carlo integration is firmly established as the basis for most practical realistic image synthesis algorithms because of its flexibility and generality. However, the visual quality of rendered images often suffers from estimator variance, which appears as visually distracting noise. Adaptive sampling and reconstruction algorithms reduce variance by controlling the sampling density and aggregating samples in a reconstruction step, possibly over large image regions. In this paper we survey recent advances in this area. We distinguish between “a priori” methods that analyze the light transport equations and derive sampling rates and reconstruction filters from this analysis, and “a posteriori” methods that apply statistical techniques to sets of samples to drive the adaptive sampling and reconstruction process. They typically estimate the errors of several reconstruction filters, and select the best filter locally to minimize error. We discuss advantages and disadvantages of recent state‐of‐the‐art techniques, and provide visual and quantitative comparisons. Some of these techniques are proving useful in real‐world applications, and we aim to provide an overview for practitioners and researchers to assess these approaches. In addition, we discuss directions for potential further improvements.