gebhart/patrepeval huggingface dataset:
Endosomal signaling of delta opioid receptors is an endogenous mechanism and therapeutic target for relief from inflammatory pain (2020)

Whether G protein-coupled receptors signal from endosomes to control important pathophysiological processes and are therapeutic targets is uncertain. We report that opioids from the inflamed colon activate δ-opioid receptors (DOPr) in endosomes of nociceptors. Biopsy samples of inflamed colonic mucosa from patients and mice with colitis released opioids that activated DOPr on nociceptors to cause a sustained decrease in excitability. DOPr agonists inhibited mechanically sensitive colonic nociceptors. DOPr endocytosis and endosomal signaling by protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) pathways mediated the sustained inhibitory actions of endogenous opioids and DOPr agonists. DOPr agonists stimulated the recruitment of Gα<sub>i/o</sub> and β-arrestin1/2 to endosomes. Analysis of compartmentalized signaling revealed a requirement of DOPr endocytosis for activation of PKC at the plasma membrane and in the cytosol and ERK in the nucleus. We explored a nanoparticle delivery strategy to evaluate whether endosomal DOPr might be a therapeutic target for pain. The DOPr agonist DADLE was coupled to a liposome shell for targeting DOPr-positive nociceptors and incorporated into a mesoporous silica core for release in the acidic and reducing endosomal environment. Nanoparticles activated DOPr at the plasma membrane, were preferentially endocytosed by DOPr-expressing cells, and were delivered to DOPr-positive early endosomes. Nanoparticles caused a long-lasting activation of DOPr in endosomes, which provided sustained inhibition of nociceptor excitability and relief from inflammatory pain. Conversely, nanoparticles containing a DOPr antagonist abolished the sustained inhibitory effects of DADLE. Thus, DOPr in endosomes is an endogenous mechanism and a therapeutic target for relief from chronic inflammatory pain.
WCMP (2014)

Data Center topologies employ multiple paths among servers to deliver scalable, cost-effective network capacity. The simplest and the most widely deployed approach for load balancing among these paths, Equal Cost Multipath (ECMP), hashes flows among the shortest paths toward a destination. ECMP leverages uniform hashing of balanced flow sizes to achieve fairness and good load balancing in data centers. However, we show that ECMP further assumes a balanced, regular, and fault-free topology, which are invalid assumptions in practice that can lead to substantial performance degradation and, worse, variation in flow bandwidths even for same size flows.
Combined Anti-Angiogenic Therapy Targeting PDGF and VEGF Receptors Lowers the Interstitial Fluid Pressure in a Murine Experimental Carcinoma (2009)

Elevation of the interstitial fluid pressure (IFP) of carcinoma is an obstacle in treatment of tumors by chemotherapy and correlates with poor drug uptake. Previous studies have shown that treatment with inhibitors of platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) signaling lowers the IFP of tumors and improve chemotherapy. In this study, we investigated whether the combination of PDGFR and VEGFR inhibitors could further reduce the IFP of KAT-4 human carcinoma tumors. The tumor IFP was measured using the wick-in-needle technique. The combination of STI571 and PTK/ZK gave an additive effect on the lowering of the IFP of KAT-4 tumors, but the timing of the treatment was crucial. The lowering of IFP following combination therapy was accompanied by vascular remodeling and decreased vascular leakiness. The effects of the inhibitors on the therapeutic efficiency of Taxol were investigated. Whereas the anti-PDGF and anti-VEGF treatment did not significantly inhibit tumor growth, the inhibitors enhanced the effect of chemotherapy. Despite having an additive effect in decreasing tumor IFP, the combination therapy did not further enhance the effect of chemotherapy. Simultaneous targeting of VEGFR and PDGFR kinase activity may be a useful strategy to decrease tumor IFP, but the timing of the inhibitors should be carefully determined.
On Expected Neighbor Discovery Time With Prior Information: Modeling, Bounds and Optimization (2017)

Neighbor discovery (ND) is an essential prerequisite for any peer-to-peer communication. In general, minimizing the discovery time is the goal for ND schemes. In this paper, we study the average discovery time for directional random ND when nodes have prior information about their set of possible neighbors, which also helps identify the performance limits of random ND schemes. Typically, discovery time analysis is done for assumptions that simplify the network structure, such as uniform neighbor relations for all nodes. However, with prior information the directional transmission probabilities depend on the node and the direction. This complicates the analysis of the expected discovery time. We first provide a closed-form expression for the expected discovery time based on the non-uniform coupon collector problem. Next, we identify directional transmission probabilities of each node that achieve a small discovery time. Due to the mathematical complexity, we provide a lower and an upper bound on the expected discovery time, which allows us to write the problem as a convex optimization problem. Through simulations, we demonstrate the performance gain due to prior knowledge with the proposed methods as compared with when no prior information is available, as well as the impact of uncertainty in the prior knowledge.
Bioactive Compounds from the Mushroom-Forming Fungus Chlorophyllum molybdites (2023)

A novel compound (<b>1</b>) along with two known compounds (<b>2</b> and <b>3</b>) were isolated from the culture broth of <i>Chlorophyllum molybdites</i>, and three known compounds (<b>4</b>-<b>6</b>) were isolated from its fruiting bodies. The planar structure of <b>1</b> was determined by the interpretation of spectroscopic data. By comparing the specific rotation of the compound with that of the analog compound, the absolute configuration of <b>1</b> was determined to be <i>R</i>. This is the first time that compounds <b>2</b>-<b>4</b> were isolated from a mushroom-forming fungus. Compound <b>2</b> showed significant inhibition activity against Axl and immune checkpoints (PD-L1, PD-L2). In the bioassay to examine growth inhibitory activity against the phytopathogenic bacteria <i>Peptobacterium carotovorum</i>, <i>Clavibacter michiganensis</i> and <i>Burkholderia glumae</i>, compounds <b>2</b> and <b>3</b> inhibited the growth of <i>P. carotovorum</i> and <i>C. michiganensis.</i> In the bioassay to examine plant growth regulatory activity, compounds <b>1</b>-<b>4</b> showed a significant regulatory activity on lettuce growth.
Covalent Triazine Polymer–Fe3O4 Nanocomposite for Strontium Ion Removal from Seawater (2017)

A microporous covalent triazine polymer (CTP) is synthesized via a Friedel–Crafts reaction and used as a solid support to immobilize magnetite Fe3O4 nanoparticles. Thermogravimetric analysis shows that approximately 60 wt % Fe3O4 is loaded onto the composite, and transmission electron microscopy analysis illustrates that the Fe3O4 nanoparticles are uniformly impregnated into the CTP surface. The CTP–Fe3O4 nanocomposite is an efficient adsorbent for the removal of strontium ion (Sr2+) from seawater. Response surface methodology, employed to optimize the removal of Sr2+, confirms that the optimal conditions for this removal are 0.55 mg, pH 7, 40 °C, and 250 min. The experimental results illustrate that the adsorption process fits well with the Freundlich isotherm, with a correlation coefficient of 0.976 and a maximum adsorption capacity of 128 mg g–1. The kinetic study demonstrates that the adsorption behavior follows pseudo-second-order kinetics. The adsorbent is easily recovered from seawater using an external magnetic field, thereby offering facile and economic separation of the adsorbent.
Trace gas detection using near-infrared diode lasers (2002)

Visible/near-infrared diode lasers are well-suited for use as spectroscopic light sources in detection of a wide variety of gases by measurement of optical absorption. The high spectral resolution of these devices permits the selective detection of targeted species, while their characteristics of room temperature operation and compatibility with fiber optics make them attractive for instrument development. The nominal range of available wavelengths includes absorption bands of numerous gas species that need to be monitored to meet various industrial objectives. While the molecular absorption bands in this spectral region consist mostly of relatively weak overtone or combination bands (some electronic bands are accessible at the shorter wavelengths), detection sensitivities of about 1 ppm-meter or better can be achieved for many gases using frequency or wavelength modulation techniques that permit routine measurement of small optical absorbances. Subppm measurement sensitivities are easily achieved using simple optical multipass designs if necessary. Diode laser-based instruments for measurement of some of these species in process control or environmental monitoring applications are now commercially available. The paper describes recent progress in development of diode laser-based trace gas measurement by presenting two examples: measurement of trace moisture contamination in high purity process gases and perimeter monitoring of a toxic gas in a refinery environment.
Reconfigurable WDM networks: systems and enabling technologies research (1996)

Summary form only given. Wavelength-division multiplexing (WDM) is a scheme in which many independent wavelength channels are simultaneously transmitted on a single fiber, with each channel located at a unique wavelength. Such a transmission scheme efficiently utilizes the available fiber bandwidth, increasing the aggregate system capacity and throughput over that of existing fiber systems and networks. Furthermore, local- and wide-area networks can achieve increased capacity and functionality by incorporating wavelength-dependent routing. In this presentation, recent progress in dynamically reconfigurable WDM networks will be described.
Processing of central and reflex vagal drives by rat cardiac ganglion neurones: an intracellular analysis (2011)

Cardiac vagal tone is an important indicator of cardiovascular health, and its loss is an independent risk factor for arrhythmias and mortality. Several studies suggest that this loss of vagal tone can occur at the cardiac ganglion but the factors affecting ganglionic transmission in vivo are poorly understood. We have employed a novel approach allowing intracellular recordings from functionally connected cardiac vagal ganglion cells in the working heart-brainstem preparation. The atria were stabilised in situ preserving their central neural connections, and ganglion cells (n = 32) were impaled with sharp microelectrodes. Cardiac ganglion cells with vagal synaptic inputs (spontaneous, n = 10; or electrically evoked from the vagus, n = 3) were identified as principal neurones and showed tonic firing responses to current injected to their somata. Cells lacking vagal inputs (n = 19, presumed interneurones) were quiescent but showed phasic firing responses to depolarising current. In principal cells the ongoing action potentials and EPSPs exhibited respiratory modulation, with peak frequency in post-inspiration. Action potentials arose from unitary EPSPs and autocorrelation of those events showed that each ganglion cell received inputs from a single active preganglionic source. Peripheral chemoreceptor, arterial baroreceptor and diving response activation all evoked high frequency synaptic barrages in these cells, always from the same single preganglionic source. EPSP amplitudes showed frequency dependent depression, leading to more spike failures at shorter inter-event intervals. These findings indicate that rather than integrating convergent inputs, cardiac vagal postganglionic neurones gate preganglionic inputs, so regulating the proportion of central parasympathetic tone that is transmitted on to the heart.
Vertebral artery stenting (2001)

The safety and efficacy of endoluminal stenting in treating atherosclerotic vertebral artery disease was evaluated in 38 vessels in 32 patients. Indications for revascularization included diplopia (n = 4), blurred vision (n = 4), dizziness (n = 23), transient ischemic attacks (n = 4), drop attack (n = 1), gait disturbance (n = 1), headache (n = 2), and asymptomatic critical stenosis (n = 1). Success (< 20% residual diameter stenosis, without stroke or death) was achieved in all 32 patients (100%). One patient experienced a transient ischemic attack (TIA) 1 hr after the procedure. At follow-up (mean, 10.6 months), all patients (100%) were alive and 31/32 (97%) were asymptomatic. One patient (3%) had in-stent restenosis at 3.5 months and underwent successful balloon angioplasty. Endoluminal stenting of vertebral artery lesions is safe, effective, and durable as evidenced by the low recurrence rate. Primary stent placement is an attractive option for atherosclerotic vertebral artery stenotic lesions. Cathet Cardiovasc Intervent 2001;54:1-5.
9th Workshop on Compiler-Driven Performance (2010)

As computer hardware continues to dramatically improve in transistor density and raw capability, the importance of compilers to bridge the gap between high-level programming languages and these abundant hardware resources has never been greater. The workshop on Compiler-Driven Performance provided an important opportunity for academic faculty, students, and industry researchers and developers from across Canada and the United States to meet to discuss the state-of-the-art in compiler technology as well as new innovations and future directions.
Telomerase Inhibition and Human Telomeric G-Quadruplex DNA Stabilization by a β-Carboline–Benzimidazole Derivative at Low Concentrations (2017)

Guanine rich regions in DNA, which can form highly stable secondary structures, namely, G-quadruplex or G4 DNA structures, affect DNA replication and transcription. Molecules that stabilize G4 DNA have become important in recent years. In this study, G4 DNA stabilization, inhibition of telomerase, and anticancer activity of synthetic β-carboline-benzimidazole derivatives (5a, 5d, 5h, and 5r) were studied. Among them, derivatives containing a 4-methoxyphenyl ring at C<sub>1</sub> and a 6-methoxy-substituted benzimidazole at C<sub>3</sub> (5a) were found to stabilize telomeric G-quadruplex DNA efficiently. The stoichiometry and interaction of a synthetic, β-carboline-benzimidazole derivative, namely, 3-(6-methoxy-1H-benzo[d]imidazol-2-yl)-1-(4-methoxyphenyl)-9H-pyrido[3,4-b]indole (5a), with human intermolecular G-quadruplex DNA at low concentrations were examined using electrospray ionization mass spectrometry. Spectroscopy techniques indicate that 5a may intercalate between the two stacks of G-quadruplex DNA. This model is supported by docking studies. When cancer cells are treated with 5a, the cell cycle arrest occurs at the sub-G<sub>1</sub> phase. In addition, an apoptosis assay and fluorescence microscopy studies using cancer cells indicate that 5a can induce apoptosis. Results of biochemical assays such as the polymerase chain reaction stop assay and telomerase activity assay indicate that 5a has the potential to stabilize G-quadruplex DNA, and thereby, it may interfere with in vitro DNA synthesis and decrease telomerase activity. The results of this study reveal that the β-carboline-benzimidazole derivative (5a) is efficient in G-quadruplex DNA stabilization over double-stranded DNA, inhibits telomerase activity, and induces apoptosis in cancer cells.
INMEX—a web-based tool for integrative meta-analysis of expression data (2013)

The widespread applications of various 'omics' technologies in biomedical research together with the emergence of public data repositories have resulted in a plethora of data sets for almost any given physiological state or disease condition. Properly combining or integrating these data sets with similar basic hypotheses can help reduce study bias, increase statistical power and improve overall biological understanding. However, the difficulties in data management and the complexities of analytical approaches have significantly limited data integration to enable meta-analysis. Here, we introduce integrative meta-analysis of expression data (INMEX), a user-friendly web-based tool designed to support meta-analysis of multiple gene-expression data sets, as well as to enable integration of data sets from gene expression and metabolomics experiments. INMEX contains three functional modules. The data preparation module supports flexible data processing, annotation and visualization of individual data sets. The statistical analysis module allows researchers to combine multiple data sets based on P-values, effect sizes, rank orders and other features. The significant genes can be examined in functional analysis module for enriched Gene Ontology terms or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, or expression profile visualization. INMEX has built-in support for common gene/metabolite identifiers (IDs), as well as 45 popular microarray platforms for human, mouse and rat. Complex operations are performed through a user-friendly web interface in a step-by-step manner. INMEX is freely available at http://www.inmex.ca.
Nonparametric inverse probability weighted estimators based on the highly adaptive lasso (2020)

Inverse probability weighted estimators are the oldest and potentially most commonly used class of procedures for the estimation of causal effects. By adjusting for selection biases via a weighting mechanism, these procedures estimate an effect of interest by constructing a pseudo-population in which selection biases are eliminated. Despite their ease of use, these estimators require the correct specification of a model for the weighting mechanism, are known to be inefficient, and suffer from the curse of dimensionality. We propose a class of nonparametric inverse probability weighted estimators in which the weighting mechanism is estimated via undersmoothing of the highly adaptive lasso, a nonparametric regression function proven to converge at $n^{-1/3}$-rate to the true weighting mechanism. We demonstrate that our estimators are asymptotically linear with variance converging to the nonparametric efficiency bound. Unlike doubly robust estimators, our procedures require neither derivation of the efficient influence function nor specification of the conditional outcome model. Our theoretical developments have broad implications for the construction of efficient inverse probability weighted estimators in large statistical models and a variety of problem settings. We assess the practical performance of our estimators in simulation studies and demonstrate use of our proposed methodology with data from a large-scale epidemiologic study.
Model-carrying code (2003)

This paper presents a new approach called model-carrying code (MCC) for safe execution of untrusted code. At the heart of MCC is the idea that untrusted code comes equipped with a concise high-level model of its security-relevant behavior. This model helps bridge the gap between high-level security policies and low-level binary code, thereby enabling analyses which would otherwise be impractical. For instance, users can use a fully automated verification procedure to determine if the code satisfies their security policies. Alternatively, an automated procedure can sift through a catalog of acceptable policies to identify one that is compatible with the model. Once a suitable policy is selected, MCC guarantees that the policy will not be violated by the code. Unlike previous approaches, the MCC framework enables code producers and consumers to collaborate in order to achieve safety. Moreover, it provides support for policy selection as well as enforcement. Finally, MCC makes no assumptions regarding the inherent risks associated with untrusted code. It simply provides the tools that enable a consumer to make informed decisions about the risk that he/she is willing to tolerate so as to benefit from the functionality offered by an untrusted application.
Implementation of a Photonic Page Buffer Based on GaAs MQW Modulators Bonded Directly over Active Silicon VLSI Circuits (1995)

The tremendous progress in high performance Very-Large Scale Integrated circuit (VLSI) technology has made possible the incorporation of several million transistors onto a single silicon chip with on-chip clock rates of 200 MegaHertz (MHz). By the end of decade, the integration density for silicon Complementary Metal Oxide Semiconductor (CMOS) is expected to be over 20 million transistors and the projected on-chip clock rate is 500 MHz. This enormous bandwidth that will be available for computation and switching on a silicon integrated circuit will create a huge bottleneck for Input and Output (I/O) to the VLSI circuit. Technologies that are being developed at AT&amp;T Bell Laboratories, now exist for attaching GaAs Multiple Quantum Well (MQW) photodetectors and light-modulators onto a prefabricated silicon integrated circuit using a well-established hybrid flip-chip bonding technique followed by substrate removal of the GaAs chip to allow surface-normal operation of the optical modulators at 850nm [1]. From a systems point of view, the demands made of optoelectronic integration method are (i) that the silicon integrated circuit be state-of-the-art, (ii) the circuit be unaffected by the integration process, (iii) that the design and optimization of the circuit proceed independently of the placement and bonding to the optical I/O. The first two goals have been achieved in reference 1, and this technique has been effectively applied to simple switching nodes for a smart-pixel based photonic switch in reference 2. In this paper we further achieve the third goal by demonstrating for the first time that modulators can be bonded directly above active submicron CMOS transistors (figure 1), and by applying the technique to the demonstration of a high-density 2Kbit first-in first-out (Fifo) page buffer circuit.