gebhart/patrepeval huggingface dataset:
Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin (2011)

Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC). While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described. Here, we describe a new inhibitor of bitter taste receptors, p-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action. Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans. Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays. We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism. Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin. Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs. Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function. Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans. This work identifies probenecid as a pharmacological tool for understanding the cell biology of bitter taste and as a lead for the development of broad specificity bitter blockers to improve nutrition and medical compliance.
Metastasis-Suppressing Potential of Ribonucleotide Reductase Small Subunit p53R2 in Human Cancer Cells (2006)

Opposite regulation of hRRM2 and p53R2 in invasion potential might play a critical role in determining the invasion and metastasis phenotype in cancer cells. The expression level of ribonucleotide reductase small subunits may serve as a biomarker to predict the malignancy potential of human cancers in the future.
The role of back contact patterning on stability and performance of Si IBC heterojunction solar cells (2014)

Interdigitated back contact (IBC) Si heterojunction solar cell initial performance and stability over time exhibits a critical dependence on the patterning processes, especially in defining the gap structure between emitter and base contacts. Patterning processes using photoresist can result in degradation even with dark storage in a dry environment over days, while other processes using a-SiN <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X</sub> :H for patterning yield stable devices over months. Use of photoresist (PR) as a mask in PECVD to form interdigitated contacts results in a gap that is insufficiently passivated and leads to cell degradation. Use of a-SiN <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">X</sub> :H as a mask creates a multi-layer gap structure which improves the cell performance and stability. The laser fired base contact (LFC) reduces V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OC</sub> slightly due to increased recombination loss, but does not cause additional instability. A stable efficiency of 17.9% was achieved in an IBC-Si heterojunction solar cell using all low temperature processes that incorporated a multi-layer gap passivation structure.
The Geometry of Multiple Images (2001)

This book formalizes and analyzes the relations between multiple views of a scene from the perspective of various types of geometries. A key feature is that it considers Euclidean and affine geometries as special cases of projective geometry. Over the last forty years, researchers have made great strides in elucidating the laws of image formation, processing, and understanding by animals, humans, and machines. This book describes the state of knowledge in one subarea of vision, the geometric laws that relate different views of a scene. Geometry, one of the oldest branches of mathematics, is the natural language for describing three-dimensional shapes and spatial relations. Projective geometry, the geometry that best models image formation, provides a unified framework for thinking about many geometric problems are relevant to vision. The book formalizes and analyzes the relations between multiple views of a scene from the perspective of various types of geometries. A key feature is that it considers Euclidean and affine geometries as special cases of projective geometry. Images play a prominent role in computer communications. Producers and users of images, in particular three-dimensional images, require a framework for stating and solving problems. The book offers a number of conceptual tools and theoretical results useful for the design of machine vision algorithms. It also illustrates these tools and results with many examples of real applications.
Non-Darcy Flow in Hydraulic Fractures: Does It Really Matter? (2005)

Abstract In recent years, non-Darcy flow has seen a significant increase in interest in the petroleum industry, especially in flow in fractures—both artificial and natural. In hydraulic fracture stimulation, non-Darcy flow can have a major impact on the reduction of a propped half-length to a considerably shorter "effective" half-length, thus lowering the well's productive capability and overall reserve recovery. These non-Darcy flow effects in propped fractures have been typically associated with high flow rates in both oil and gas wells. This paper shows that non-Darcy flow effects have an impact on the performance of a hydraulically fractured well even at low flow rates. Although not as drastic as the effects on high flow rate wells, reductions in flow capacity of 5-30% can be realized in low rate wells. Such reductions are due solely to non-Darcy effects. When combined with other concerns, such as multiphase flow, the production reduction effects are even greater. Development of a simple spreadsheet is provided to aid engineers in assessing the impact non-Darcy flow may have in a given situation. The spreadsheet is not intended to replace more in-depth investigation of non-Darcy flow effects but instead provides a conduit to assess the sensitivity of certain parameters in a hydraulic fracture stimulation situation. For comparison purposes, results of the loss in long-term dynamic conductivity on well performance and cumulative gas recovery over time in low permeability reservoirs are also presented. These calculations were performed using dynamic conductivity loss calculations coupled with a transient gas reservoir simulator. These results showed that for the cases examined, non-Darcy effects could reduce cumulative gas production by up to 18.1% over a ten-year period.
Norepinephrine involvement in antidepressant action. (2000)

Because of the introduction and popularity of the selective serotonin reuptake inhibitor (SSRI) antidepressants, much attention was centered on the indolealkylamine 5-hydroxytryptamine, or serotonin. To some extent, this focus on serotonin occurred at the expense of the catecholamine neurotransmitter norepinephrine. Nevertheless, it has been apparent for almost 40 years that selective blockers of norepinephrine reuptake may be antidepressants (e.g., desipramine). This brief review covers the acute pharmacologic effects that may be responsible for the efficacy of currently marketed antidepressants as well as that of reboxetine, a newly developed selective norepinephrine reuptake inhibitor. Also discussed is the fact that the acute pharmacologic profile of selective reuptake inhibitors often predicts effects they produce when given long term. For example, the long-term administration of SSRIs produces certain effects on serotonergic systems, but not noradrenergic ones. By contrast, selective norepinephrine reuptake inhibitors, when given long term, modify certain noradrenergic parameters, but not serotonergic indices. Finally, it is speculated how drugs that enhance central noradrenergic transmission might ameliorate the symptoms of depression.
Single-mode collapse in 6328-Å He–Ne lasers (1978)

Internal-mirror 6328-A He-Ne lasers have an intramode frequency difference when placed in a transverse magnetic field. When the magnetic field strength is increased until the Zeeman frequency shift approaches the mode spacing, mode coupling is nduced. In some multimode lasers, this mode coupling results in a collapse into single-mode operation with no loss of over-all laser power in the output. The intramode frequency difference can be exploited to produce a simple frequency stabilization system whose frequency variation is less than 1 part in 10(10). Plots of beat frequency variation and single-mode tuning range are included.
Optimization of fiber-coupled laser-diode end-pumped lasers: influence of pump-beam quality (1996)

A general model has been developed for the optimization of fiber-coupled laser-diode pumped lasers by including the effect of pump-beam quality into the mode-overlap integrals. The numerical results of the mode-overlap integrals have been fitted to an analytical function of pump spot size, laser mode size and the parameter /spl beta/, which is in terms of laser-diode beam quality and properties of the active medium. This analytical function allowed us to obtain explicit formulae for the threshold pump power, the slope efficiency, and the optimum pump spot size. With these formulae, the optimum mode size and the maximum output efficiency can be easily calculated for arbitrary values of /spl beta/ and input power. From the numerical results, we obtained an analytical expression to relate the required input power and pump-beam quality to the desired output efficiency and properties of an active medium. The present model provides a straightforward procedure to design the laser resonator and the optical coupling system for optimization. To illustrate the utility of the present model, a Nd:YAG laser pumped by fiber-coupled laser diodes is considered and optimized.
Holmium-Loaded Poly(<scp>l</scp>-lactic Acid) Microspheres:  In Vitro Degradation Study (2006)

The clinical application of holmium-loaded poly(l-lactic acid) (PLLA) microspheres for the radionuclide treatment of liver malignancies requires in depth understanding of the degradation characteristics of the microspheres. To this end, an in-vitro degradation study was conducted. PLLA-microspheres with and without HoAcAc loading, and before and after neutron or gamma irradiation, were incubated in a phosphate buffer at 37 °C for 12 months. In contrast with the other microsphere formulations, only the neutron-irradiated Ho-PLLA-MS disintegrated. At the end of the experiment (52 weeks) highly crystalline fragments, as evidenced from Differential Scanning Calorimetry, were present. Infrared spectroscopy showed that these fragments consisted of holmium lactate. In conclusion, this study demonstrates that the degradation of neutron-irradiated Ho-PLLA-MS was substantially accelerated by the HoAcAc incorporation and subsequent neutron irradiation. The degradation of these microspheres in aqueous solution resulted in the formation of insoluble holmium lactate microcrystals without release of Ho3+.
Internalization and desensitization of adenosine receptors (2007)

Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A(1), A(2A), A(2B) and A(3) receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body and involved in a variety of physiological processes and diseases, there is great interest in understanding how the different subtypes are regulated, as a basis for designing therapeutic drugs that either avoid or make use of this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein-coupled receptor kinases (GRKs), a process that is followed by binding of arrestin proteins. This prevents receptors from activating downstream heterotrimeric G protein pathways, but at the same time allows activation of arrestin-dependent signalling pathways. Upon agonist treatment, adenosine receptor subtypes are differently regulated. For instance, the A(1)Rs are not (readily) phosphorylated and internalize slowly, showing a typical half-life of several hours, whereas the A(2A)R and A(2B)R undergo much faster downregulation, usually shorter than 1 h. The A(3)R is subject to even faster downregulation, often a matter of minutes. The fast desensitization of the A(3)R after agonist exposure may be therapeutically equivalent to antagonist occupancy of the receptor. This review describes the process of desensitization and internalization of the different adenosine subtypes in cell systems, tissues and in vivo studies. In addition, molecular mechanisms involved in adenosine receptor desensitization are discussed.
Optimal projection for multidimensional signal detection (2003)

The author derives the projection method which maximises the probability of signal detection for a fixed probability of false alarm. Samples containing signal plus noise and noise alone are assumed to have independent, identically distributed distributions, but are otherwise arbitrary. Only one sample in the set of samples projected onto a single sample may contain the signal. Performance of the optimal projection technique is compared with two simpler techniques-maximum value projection and summation projection.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Decreased neutrophil respiratory burst on exposure to cobalt‐chrome alloy and polystyrene <i>in vitro</i> (1992)

The effect of biomaterials on the superoxide-producing ability of neutrophils was studied. Human peripheral blood neutrophils were incubated with cobalt-base alloy (F-75) or polystyrene beads of a nonphagocytosable size. Respiratory burst activity was studied by measuring superoxide dismutase inhibitable reduction of cytochrome C. Neutrophils were found to release no more superoxide anion on incubation for up to 3 h with either material in a protein-free medium than controls without foreign material. However, the ability of neutrophils incubated with either biomaterial to subsequently respond to phorbol myristate acetate challenge was decreased (p less than 0.05). Chemical analysis of supernatants for the F-75 samples showed a high concentration of cobalt in the medium within 1 h of incubation. Minimal chromium and nickel was detected. No correlation could be demonstrated between metal in solution and the respiratory burst defect in neutrophils. Instead it appears that interaction of cells with either surface was the critical event in altering the response to phorbol myristate acetate. This observed functional defect may play an important role in rendering tissue around implanted biomaterials susceptible to infections.
Opioid and anti‐opioid peptides (1995)

The numerous endogenous opioid peptides (beta-endorphin, enkephalins, dynorphins ... ) and the exogenous opioids (such as morphine) exert their effects through the activation of receptors belonging to four main types, mu, delta, kappa and epsilon. Opioidergic neurones and opioid receptors are largely distributed centrally and peripherally. It is thus not surprising that opioids have numerous pharmacological effects and that endogenous opioids are thought to be involved in the physiological control of various functions, among which nociception is particularly emphasized. Some opioid targets may be components of homeostatic systems tending to reduce the effects of opioids. "Anti-opioid" properties have been attributed to various peptides, especially cholecystokinin (CCK), neuropeptide FF (NPFF) and melanocyte inhibiting factor (MIF)-related peptides. In addition, a particular place should be attributed, paradoxically, to opioid peptides themselves among the anti-opioid peptides. These peptides can oppose some of the acute effects of opioids, and a hyperactivation of anti-opioid peptidergic neurones due to the chronic administration of opioids may be involved in the development of opioid tolerance and/or dependence. In fact, CCK, NPFF and the MIF family of peptides have complex properties and can act as opioid-like as well as anti-opioid peptides. Thus, "opioid modulating peptides" would be a better term to designate these peptides, which probably participate, together with the opioid systems, in multiple feed-back loops for the maintenance of homeostasis. "Opioid modulating peptides" have generally been shown to act through the activation of their own receptors. For example, CCK appears to exert its anti-opioid actions mainly through the activation of CCK-B receptors, whereas its opioid-like effects seem to result from the stimulation of CCK-A receptors. However, the partial agonistic properties at opioid receptors of some MIF-related peptides very likely contribute to their ability to modulate the effects of opioids. CCK- and NPFF-related drugs have potential therapeutic interest as adjuncts to opioids for alleviating pain and/or for the treatment of opioid abuse.
Evolving toward the next-generation Internet: challenges in the path forward (2002)

Most people would agree that the Internet is one of the great technical and business success stories of the 20th century, notwithstanding the financial losses that have been experienced by overly optimistic and speculative investors. Even in the context of the current dramatic slowdown in telecommunications investment, the Internet and its supported applications are continuing to revolutionize almost all aspects of our business and personal lives - mostly for the better. The author reviews a subset of the challenges that lie ahead in evolving the Internet to meet the growing and changing needs of its users.
Percutaneous Acetic Acid Injection for Hepatocellular Carcinoma: Using CT Fluoroscopy to Evaluate Distribution of Acetic Acid Mixed with an Iodinated Contrast Agent (2003)

Monitoring acetic acid distribution on CT fluoroscopy can detect extratumoral diffusion and may optimize the distribution of acetic acid in hepatocellular carcinoma.
Comprehensive Privacy Analysis of Deep Learning: Passive and Active White-box Inference Attacks against Centralized and Federated Learning (2019)

Deep neural networks are susceptible to various inference attacks as they remember information about their training data. We design white-box inference attacks to perform a comprehensive privacy analysis of deep learning models. We measure the privacy leakage through parameters of fully trained models as well as the parameter updates of models during training. We design inference algorithms for both centralized and federated learning, with respect to passive and active inference attackers, and assuming different adversary prior knowledge. We evaluate our novel white-box membership inference attacks against deep learning algorithms to trace their training data records. We show that a straightforward extension of the known black-box attacks to the white-box setting (through analyzing the outputs of activation functions) is ineffective. We therefore design new algorithms tailored to the white-box setting by exploiting the privacy vulnerabilities of the stochastic gradient descent algorithm, which is the algorithm used to train deep neural networks. We investigate the reasons why deep learning models may leak information about their training data. We then show that even well-generalized models are significantly susceptible to white-box membership inference attacks, by analyzing state-of-the-art pre-trained and publicly available models for the CIFAR dataset. We also show how adversarial participants, in the federated learning setting, can successfully run active membership inference attacks against other participants, even when the global model achieves high prediction accuracies.
Pathophysiology and epidemiology of hemophagocytic lymphohistiocytosis (2015)

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by extreme immune activation, resulting in pathologic inflammation. The diagnosis includes a spectrum of inherited or acquired defects in cytotoxic lymphocyte function, often with uncontrolled infections. HLH may also arise as the result of persistent antigen stimulation due to autoimmune disease or malignancy. HLH is often described in binary terms as "primary," indicating Mendelian inheritance of gene mutations resulting in cytotoxic lymphocyte dysfunction, or "secondary" indicating an acquired reactive disorder. Increasing evidence describes HLH as more complex phenomenon, resulting from specific immune challenges in patients with a susceptible genetic background. Early recognition of HLH and evaluation of potential causes is critically important, as survival generally requires urgent treatment with immune suppression and resolution of the activating antigen. However, the diagnosis of HLH is challenged by the myriad of pathways that lead to pathologic inflammation and the clinical overlap with other conditions. Further improvements in therapy will require prospective trials to define optimal strategies for each patient based on the individual paths that lead to pathologic inflammation.
On the presence of aluminum in thermally grown oxides on 6H-silicon carbide [power MOSFETs] (1996)

N-type and P-type 6H-Silicon carbide wafers, along with P-type silicon control wafers were oxidized in dry oxygen at 1275/spl deg/C for 45 min. Capacitance-voltage measurements on the SiO/sub 2/ films formed on the N-type 6H-SiC and the silicon control wafers yielded near ideal characteristics while the SiO/sub 2/ films on P-type 6H-SiC revealed high effective charge and interface state densities. Secondary Ion Mass Spectroscopy performed on the oxides showed significant levels of aluminum and sodium in SiO/sub 2/ on both N-type and P-type 6H-SiC but not on the silicon control wafers indicating that neither element was introduced during processing. The presence of aluminum in oxides on both types suggests that it is not solely responsible for the increased effective oxide charge and interface state densities commonly observed in oxides formed on P-type 6H-SiC.
Characterization and improvement of interferon-[gamma] glycosylation in Chinese hamster ovary cell culture (1997)

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1997.