gebhart/patrepeval huggingface dataset:
ChemInform Abstract: Synthesis of 2′′‐Amino‐2′′‐deoxyarbekacin and Its Analogues Having Potent Activity Against Methicillin‐Resistant Staphylococcus aureus. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Planning Large-scale Object Rearrangement Using Deep Reinforcement Learning (2022)

Object rearrangement is about moving a set of objects from an initial state to a goal state through task and motion planning. Existing methods either show poor scalability in number of objects they can handle, or do not generalize well across situations, or need explicit running buffers to avoid collisions during placements. In this paper, we propose a deep-RL based task planning method to solve large-scale object rearrangement problems. Given the source and target state of objects in the form of images, our method determines a collision-free object movement plan. Our method produces a feasible plan in discrete-continuous action space where picking the selected objects are discrete actions followed by a set of continuous actions to place the object. We propose a novel hierarchical dense reward structure to train our deep-RL network to make our method more sample efficient using the AI2Thor simulator. We show that our method works well on unseen publicly available datasets and on a publicly available simulation environment such as Pybullet thereby demonstrating the superiority of our method in terms of generalizability. To the best of our knowledge, our method is the first one that demonstrates the rearrangement across different scenarios from 2D surfaces such as tabletops to 3D rooms with a large number of objects and without any explicit need of buffer space.
Role of prostaglandin D2 and the autonomic nervous system in niacin‐induced flushing (前列腺素D2与自主神经系统在烟酸引起的脸红中的作用) (2012)

The present study indicates, for the first time, that the parasympathetic nervous system, in addition to PGD(2) , may play an important role in niacin-induced flushing. Changing the sympathetic/parasympathetic balance in favor of parasympathetic activation may be a good therapeutic target to reduce niacin-induced flushing.
Non-intrusive methods for condition assessment of distribution and transmission switchgear (2018)

JWG A3.32 with CIRED completed the Technical Brochure, which provides comprehensive information on Non-Intrusive Condition assessment of the T&D switchgear that can be applied on HV and MV circ ...
Advancing the state of mobile cloud computing (2012)

The capabilities of mobile devices have been improving very quickly in terms of computing power, storage, feature support, and developed applications. However, these mobile applications are still intrinsically limited by a relative lack of bandwidth, computing power, and energy compared to their tethered counterparts. Cloud computing offers abundant computing power that can be tapped easily. Apple iCloud and Amazon Silk browser are two recent mobile applications that leverage the cloud. In this paper, we systematically explore the fundamental research questions when combining mobile and cloud computing. We will highlight some of the challenges we face and some of the solutions we are pursuing.
A Multi-scale Computational Platform to Mechanistically Assess the Effect of Genetic Variation on Drug Responses in Human Erythrocyte Metabolism (2016)

Progress in systems medicine brings promise to addressing patient heterogeneity and individualized therapies. Recently, genome-scale models of metabolism have been shown to provide insight into the mechanistic link between drug therapies and systems-level off-target effects while being expanded to explicitly include the three-dimensional structure of proteins. The integration of these molecular-level details, such as the physical, structural, and dynamical properties of proteins, notably expands the computational description of biochemical network-level properties and the possibility of understanding and predicting whole cell phenotypes. In this study, we present a multi-scale modeling framework that describes biological processes which range in scale from atomistic details to an entire metabolic network. Using this approach, we can understand how genetic variation, which impacts the structure and reactivity of a protein, influences both native and drug-induced metabolic states. As a proof-of-concept, we study three enzymes (catechol-O-methyltransferase, glucose-6-phosphate dehydrogenase, and glyceraldehyde-3-phosphate dehydrogenase) and their respective genetic variants which have clinically relevant associations. Using all-atom molecular dynamic simulations enables the sampling of long timescale conformational dynamics of the proteins (and their mutant variants) in complex with their respective native metabolites or drug molecules. We find that changes in a protein's structure due to a mutation influences protein binding affinity to metabolites and/or drug molecules, and inflicts large-scale changes in metabolism.
Impact of Nonlinear Impairments in MDM Transmissions Using Rescaled Multimode Fibers (2019)

We show that the nonlinear impairments in mode-division multiplexing systems scale opposite to the spatial density of modes in multimode fibers with a constant numerical aperture.
A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling (2016)

Cystic fibrosis (CF)-related diabetes in humans is intimately related to exocrine pancreatic insufficiency, yet little is known about how these 2 disease processes simultaneously evolve in CF. In this context, we examined CF ferrets during the evolution of exocrine pancreatic disease. At 1 month of age, CF ferrets experienced a glycemic crisis with spontaneous diabetic-level hyperglycemia. This occurred during a spike in pancreatic inflammation that was preceded by pancreatic fibrosis and loss of β-cell mass. Surprisingly, there was spontaneous normalization of glucose levels at 2-3 months, with intermediate hyperglycemia thereafter. Mixed meal tolerance was impaired at all ages, but glucose intolerance was not detected until 4 months. Insulin secretion in response to hyperglycemic clamp and to arginine was impaired. Insulin sensitivity, measured by euglycemic hyperinsulinemic clamp, was normal. Pancreatic inflammation rapidly diminished after 2 months of age during a period where β-cell mass rose and gene expression of islet hormones, peroxisome proliferator-activated receptor-γ, and adiponectin increased. We conclude that active CF exocrine pancreatic inflammation adversely affects β-cells but is followed by islet resurgence. We predict that very young humans with CF may experience a transient glycemic crisis and postulate that pancreatic inflammatory to adipogenic remodeling may facilitate islet adaptation in CF.
An on-chip biosensor based on supercritical angle fluorescence (2021)

Supercritical angle fluorescence (SAF) is a surface sensitive detection mechanism that has been used to perform rapid, sensitive detection of biomolecules. However, the SAF biosensors that have been demonstrated so far have been either bulky and expensive or small and affordable while sacrificing on sensitivity . We present a novel interference based SAF biosensor technology that has the potential to be fast, small, inexpensive and mass manufacturable while being as sensitive as the current gold standard. This technology can therefore create biosensors in a wide range of form factors, from large, complex high multiplex devices to small handheld point of care solutions.
Visualization using ultrasonic echo signal on boiling two-phase flow (2006)

Pulse ultrasound technique has been applied to measure the reflected echo signals from vapor bubbles in boiling two-phase flow. In this study, an ultrasonic transducer, which has allowable temperature limit of 120°C, was developed for ultrasonic measurement in boiling two-phase flow under atmospheric pressure. The pulse ultrasound transmitted from an ultrasonic transducer enters into a vessel through the wall 1mm thick made of carbon steel, and echo signals are received by the same transducer. So the delay time and strength of a pulse echo is obtained from this measurement, and the effect of boiling phenomena is estimated by the echo distribution.
Immunogenicity of a Bovine Herpesvirus 1 Glycoprotein D DNA Vaccine Complexed with Bovine Neutrophil Beta-Defensin 3 (2014)

ABSTRACT Protective efficacy against bovine herpesvirus 1 (BoHV-1) has been demonstrated to be induced by a plasmid encoding bovine neutrophil beta-defensin 3 (BNBD3) as a fusion construct with truncated glycoprotein D (tgD). However, in spite of the increased cell-mediated immune responses induced by this DNA vaccine, the clinical responses of BoHV-1-challenged cattle were not reduced over those observed in animals vaccinated with the plasmid encoding tgD alone; this might have been because the vaccine failed to improve humoral responses. We hypothesized that an alternative vaccine design strategy that utilized the DNA vaccine pMASIA-tgD as a complex with BNBD3 might improve humoral responses while maintaining robust Th1-type cell-mediated responses. C57BL/6 mice were vaccinated with pMASIA-tgD complexed with 0, 0.01875, 0.1875, or 1.875 nmol of a stable synthesized analog of BNBD3 (aBNBD3). The best results were seen in mice immunized with the vaccine composed of pMASIA-tgD complexed to 0.1875 nmol aBNBD3. In this group, humoral responses were improved, as evidenced by increased virus neutralization, tgD-specific early IgG1, and later IgG2a titers, while the strong cell-mediated immune responses, measured based on specific gamma interferon (IFN-γ)-secreting cells, were maintained relative to pMASIA-tgD. Modulation of the immune response might have been due in part to the effect of BNBD3 on dendritic cells (DCs). In vitro studies showed that murine bone marrow-derived DCs (BMDCs) pretreated with aBNBD3 were activated, as evidenced by CD11c downregulation, and were functionally mature, as shown by increased allostimulatory ability. Native, synthetic, and analog forms of BNBD3 were equally capable of inducing functional maturation of BMDCs.
Pathogen effector recognition-dependent association of NRG1 with EDS1 and SAG101 in TNL receptor immunity (2020)

Abstract Plants utilise intracellular nucleotide-binding, leucine-rich repeat (NLR) immune receptors to detect pathogen effectors and activate local and systemic defence. NRG1 and ADR1 “helper” NLRs (RNLs), cooperate with enhanced disease susceptibility 1 (EDS1), senescence-associated gene 101 (SAG101) and phytoalexin-deficient 4 (PAD4) lipase-like proteins to mediate signalling from TIR domain NLR receptors (TNLs). However, the mechanism of RNL/EDS1-family protein cooperation is poorly understood. Here, we provide genetic and molecular evidence for exclusive EDS1/SAG101/NRG1 and EDS1/PAD4/ADR1 co-functions in TNL immunity. Using immunoprecipitation and mass spectrometry, we show effector recognition-dependent association of NRG1 with EDS1 and SAG101, but not PAD4. An EDS1-SAG101 complex associates with NRG1, and EDS1-PAD4 associates with ADR1, only in an immune-activated state. NRG1 requires an intact nucleotide-binding P-loop motif, and EDS1 a functional EP domain and its partner SAG101, for induced association and immunity. Thus, two distinct modules (NRG1/EDS1/SAG101 and ADR1/EDS1/PAD4) are required to execute TNL receptor defence signalling.
Reversible Lineage-Specific Priming of Human Embryonic Stem Cells Can Be Exploited to Optimize the Yield of Differentiated Cells (2015)

The clinical use of human embryonic stem cells (hESCs) requires efficient cellular expansion that must be paired with an ability to generate specialized progeny through differentiation. Self-renewal and differentiation are deemed inherent hallmarks of hESCs and a growing body of evidence suggests that initial culture conditions dictate these two aspects of hESC behavior. Here, we reveal that defined culture conditions using commercial mTeSR1 media augment the expansion of hESCs and enhance their capacity for neural differentiation at the expense of hematopoietic lineage competency without affecting pluripotency. This culture-induced modification was shown to be reversible, as culture in mouse embryonic fibroblast-conditioned media (MEF-CM) in subsequent passages allowed mTeSR1-expanded hESCs to re-establish hematopoietic differentiation potential. Optimal yield of hematopoietic cells can be achieved by expansion in mTeSR1 followed by a recovery period in MEF-CM. Furthermore, the lineage propensity to hematopoietic and neural cell types could be predicted via analysis of surrogate markers expressed by hESCs cultured in mTeSR1 versus MEF-CM, thereby circumventing laborious in vitro differentiation assays. Our study reveals that hESCs exist in a range of functional states and balance expansion with differentiation potential, which can be modulated by culture conditions in a predictive and quantitative manner.
Combating False Negatives in Adversarial Imitation Learning (2021)

In adversarial imitation learning, a discriminator is trained to differentiate agent episodes from expert demonstrations representing the desired behavior. However, as the trained policy learns to be more successful, the negative examples (the ones produced by the agent) become increasingly similar to expert ones. Despite the fact that the task is successfully accomplished in some of the agent's trajectories, the discriminator is trained to output low values for them. We hypothesize that this inconsistent training signal for the discriminator can impede its learning, and consequently leads to worse overall performance of the agent. We show experimental evidence for this hypothesis and that the ‘False Negatives’ (i.e. successful agent episodes) significantly hinder adversarial imitation learning, which is the first contribution of this paper. Then, we propose a method to alleviate the impact of false negatives and test it on the BabyAI environment. This method consistently improves sample efficiency over the baselines by at least an order of magnitude.
Fabrication of fs laser assisted optical self-writing waveguide (2008)

We developed a novel waveguide fabrication technology, i.e., femtosecond (fs) pulse laser assisted self-writing waveguide technology, to overcome problems of standard technologies, such as time consuming and high cost. Based on a light induced self-written (LISW) waveguide fabrication technology, a 488nm cw laser was launched through an optical fiber into UV curable resin. At the same time a 800nm fs laser was additionally used as a 3D position selective assistant beam. As the UV resin was cured by the 488nm laser and 800nm fs laser irradiation, a fiber/waveguide connecting 2D/3D waveguide was easily fabricated.
The Napier88 Standard Library Reference Manual (1997)

Lindane (gamma-HCH) was examined for its effect on primordial germ cell (PGC) development in the mouse embryo. We found that exposure by gavage of pregnant mice to 15 or 30 mg/kg/bw lindane during the period of PGC migration and gonad colonization (from 8.5 to 11.5 days post coitum, dpc) resulted in a significant reduction of the number of germ cells within 12.5 dpc testis and ovaries (a maximum of about 25 and 40%, respectively). Similarly, lindane caused a dose-dependent decrease of the PGC number in an in vitro culture model. Further experiments showed that in such model, lindane induced features of apoptotic cell death in PGCs such as increase in caspase-3 activity, poly-ADP-ribose polymerase cleavage, and terminal dUTP nick-end labeling (TUNEL) positivity. A marked increase of the number of PGCs positive for TUNEL staining was also observed in 12.5 dpc gonads of embryos from pregnant mice subjected one day before to acute lindane treatment (60 mg/kg/bw). Finally, we show that a brief incubation of isolated PGCs with 10(-5)M lindane resulted in a marked decrease of the basal and kit-ligand-induced phosphorylation level of the AKT kinase, known to be crucial for PGC survival. Taken together these results demonstrate that embryo exposure to lindane during early stages of gametogenesis can severely impair the number of germ cells in the fetal gonads; the compound appears to affect PGC survival through a direct proapoptotic action likely resulting from its adverse effect on AKT activity in such cells.
Fibroblast activation protein and focal adhesion kinase: novel stromal therapeutic targets in pancreatic adenocarcinoma (2004)

4094 Background: Fibroblast activation protein (FAP) is a serine protease expressed on tumor stromal fibroblasts which results in tumor growth potentiation. Focal adhesion kinase (FAK) is a protein tyrosine kinase which promotes cell growth and migration through the extracellular matrix. Given the extensive desmoplasia characteristic of pancreatic adenocarcinoma, we hypothesized that FAP and FAK would be overexpressed in pancreatic cancer and contribute to poor outcome. Methods: Twenty-nine paraffin-embedded pancreatic adenocarcinoma specimens from patients undergoing curative resection were obtained from the Fox Chase Cancer Center tumor bank. Four samples (2 normal and 2 mucinous borderline tumors) served as controls. FAP and FAK expression was assessed by immunohistochemistry and graded by staining extent (%) and intensity (0–3+). Results: Ninety percent of tumor specimens (26/29) expressed FAP in either fibroblasts surrounding tumor (FST), surrounding stroma (SS), or tumor. The highest expression level by intensity was: 3+ (14), 2+ (9), 1+ (3). A strong correlation was noted between FAP expression in FST and in SS (Pearson correlation coefficient 0.75, p<0.001). In contrast, control samples displayed no FAP expression in SS. FAK was expressed on tumor cells in all 29 samples, with three-quarters having 100% staining. In addition, median FAK expression in SS was 50%. A strong correlation was noted between percent staining of FAP and FAK in SS (Pearson correlation coefficient 0.637 (p<0.001). Conclusions: FAP is overexpressed in 90% of pancreatic adenocarcinoma specimens, with similar expression in both FST and SS. FAK is also overexpressed in SS and correlates with expression of FAP, suggesting that interaction between these proteins may contribute to pancreatic cancer invasiveness. Additional samples are being evaluated and correlation with clinical characteristics is ongoing. As targeting of FAP appears promising in preclinical models, pancreatic cancer is an excellent disease for future clinical development of stromal-directed therapeutics. No significant financial relationships to disclose.
Evaluation of efficacy of prion reduction filters using blood from an endogenously infected 263K scrapie hamster model (2015)

Leukoreduction removed the majority of infectivity from 263K scrapie hamster blood. The P-Capt filter removed a proportion of the remaining infectivity, but residual infectivity was observed in two independent processes.
Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson’s Disease Model (2017)

Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy. Here, we introduce a two-pronged treatment strategy, composed of MR image-guided focused ultrasound (FUS) and brain-penetrating nanoparticles (BPN), that provides widespread but targeted GDNF transgene expression in the brain following systemic administration. MR image-guided FUS allows circulating gene vectors to partition into the brain tissue by noninvasive and transient opening of the blood-brain barrier (BBB) within the areas where FUS is applied. Once beyond the BBB, BPN provide widespread and uniform GDNF expression throughout the targeted brain tissue. After only a single treatment, our strategy led to therapeutically relevant levels of GDNF protein content in the FUS-targeted regions in the striatum of the 6-OHDA-induced rat model of PD, which lasted at least up to 10 weeks. Importantly, our strategy restored both dopamine levels and dopaminergic neuron density and reversed behavioral indicators of PD-associated motor dysfunction with no evidence of local or systemic toxicity. Our combinatorial approach overcomes limitations of current delivery strategies, thereby potentially providing a novel means to treat PD.
alpha 2-Macroglobulin binding to cultured fibroblasts. Solubilization and partial purification of binding sites. (1983)

Binding sites having the characteristics of receptors for "activated" alpha 2-macroglobulin (alpha 2M) have been solubilized with octyl-beta-D-glucoside from fibroblast membranes. When the detergent was removed by dialysis, the resulting insoluble extract was shown to bind 125I-alpha 2M specifically. Analysis of the binding data using a nonlinear curve-fitting program suggests that the solubilized preparation contains two classes of binding sites (KD = 0.34 nM and KD = 104 nM). Membranes or solubilized extracts from KB cells which lack alpha 2M binding sites did not specifically bind 125I-alpha 2M. The solubilized binding sites from fibroblasts were inactivated by boiling and trypsin treatment, and required Ca+2 for maximal binding. In addition, the high affinity binding of 125I-alpha 2M to the solubilized receptor was inhibited by bacitracin and by alpha-bromo-5-iodo-4-hydroxy-3-nitroacetophenone, two agents which interfere with the uptake of alpha 2M in cultured fibroblasts. Using a combination of ion exchange and gel permeation chromatography, we have purified the high affinity alpha 2M binding site approximately 100-fold from membrane derived from NIH-3T3 (spontaneously transformed) fibroblasts grown as tumors in mice. The receptor is apparently an acidic protein and the receptor octyl-beta-D-glucoside complex has a Stokes radius of 45-50 A as measured by gel filtration.
Optimal operation strategies of pumped storage hydropower plant considering the integrated AC grids and new energy utilization (2022)

The large-scale development and utilization of new energy resource extremely promotes the construction and application of the flexible DC power grid especially in China. This paper focuses on the operation stability and new energy transmission of an actual regional power grid in North China, including new energy plants, the flexible DC power grid, a pumped storage hydropower plant (PSHP) with variable speed pumped storage unit (VSPSU) and regional AC power grids. According to the operation rules and goals, the economic operation model of the flexible DC-PSHP system is established by the mixed-integer second-order cone programming. Considering the transmission and consumption of the new energy generation, two operation strategies and three simulation scenarios are proposed. The day-ahead optimal operation schemes of PSHP in different scenarios are given by the case simulation. The results show that the proposed strategies can satisfy the operation demands of the regional power grid both in new energy generation transmission and operation economic benefits.
ChemInform Abstract: SYNTHESIS OF 4H‐1,2,4,6‐THIATRIAZINE 1,1‐DIOXIDE: A PRECURSOR OF 4‐CYANO‐1,2,6‐THIADIAZINE 1,1‐DIOXIDES (1984)

Abstract Das aus Sulfamid (I) und o‐Ameisensäureester (II) zugängliche Thiatriazindioxid (III) reagiert mit den Cyanessigsäurederivaten (IV) zu den Thiadjazindioxiden (V).