gebhart/patrepeval huggingface dataset:
5-HT1A and 5-HT7 receptors contribute to lurasidone-induced dopamine efflux (2012)

Lurasidone is a novel, atypical antipsychotic drug with serotonin [5-hydroxytryptamine (5-HT)]2A, 5-HT7, dopamine (DA) D2 antagonist, and 5-HT1A receptor partial agonist properties. The ability of lurasidone to reverse the effects of subchronic administration phencyclidine, to impair novel object recognition in rats, an animal model of cognitive impairment in schizophrenia, is dependent, in part, on its 5-HT1A agonist and 5-HT7 receptor antagonist properties. We tested whether 5-HT1A partial agonism or 5-HT7 antagonism, or both, contributed to the ability of lurasidone to enhance cortical and hippocampal DA efflux, which may be related to its ability to improve cognition. Here, we report that lurasidone, 0.25 and 0.5, but not 0.1 mg/kg, subcutaneously, significantly increased DA efflux in the prefrontal cortex and hippocampus in a dose-dependent manner. Lurasidone, 0.5 mg/kg, also produced a smaller increase in DA efflux in the nucleus accumbens. Pretreatment with the 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg, subcutaneously), partially blocked the lurasidone-induced cortical and hippocampal DA efflux. Further, subeffective doses of the 5-HT1A receptor agonist, tandospirone (0.2 mg/kg), or the 5-HT7 antagonist, SB269970 (0.3 mg/kg), potentiated the ability of a subeffective dose of lurasidone (0.1 mg/kg) to increase DA efflux in the prefrontal cortex. These findings suggest that the effects of lurasidone on the prefrontal cortex and hippocampus, DA efflux are dependent, at least partially, on its 5-HT1A agonist and 5-HT7 antagonist properties and may contribute to its efficacy to reverse the effects of subchronic phencyclidine treatment and improve schizophrenia.
A Novel Role for PDZ-Binding Motif of Influenza A Virus Nonstructural Protein 1 in Regulation of Host Susceptibility to Postinfluenza Bacterial Superinfections (2019)

Influenza A viruses (IAVs) have multiple mechanisms for altering the host immune response to aid in virus survival and propagation. While both type I and II interferons (IFNs) have been associated with increased bacterial superinfection (BSI) susceptibility, we found that in some cases type I IFNs can be beneficial for BSI outcome. Specifically, we have shown that antagonism of the type I IFN response during infection by some IAVs can lead to the development of deadly BSI. The nonstructural protein 1 (NS1) from IAV is well known for manipulating host type I IFN responses, but the viral proteins mediating BSI severity remain unknown. In this study, we demonstrate that the PDZ-binding motif (PDZ-bm) of the NS1 C-terminal region from mouse-adapted A/Puerto Rico/8/34-H1N1 (PR8) IAV dictates BSI susceptibility through regulation of IFN-α/β production. Deletion of the NS1 PDZ-bm from PR8 IAV (PR8-TRUNC) resulted in 100% survival and decreased bacterial burden in superinfected mice compared with 0% survival in mice superinfected after PR8 infection. This reduction in BSI susceptibility after infection with PR8-TRUNC was due to the presence of IFN-β, as protection from BSI was lost in Ifn-β<sup>-/-</sup> mice, resembling BSI during PR8 infection. PDZ-bm in PR8-infected mice inhibited the production of IFN-β posttranscriptionally, and both delayed and reduced expression of the tunable interferon-stimulated genes. Finally, a similar lack of BSI susceptibility, due to the presence of IFN-β on day 7 post-IAV infection, was also observed after infection of mice with A/TX98-H3N2 virus that naturally lacks a PDZ-bm in NS1, indicating that this mechanism of BSI regulation by NS1 PDZ-bm may not be restricted to PR8 IAV. These results demonstrate that the NS1 C-terminal PDZ-bm, like the one present in PR8 IAV, is involved in controlling susceptibility to BSI through the regulation of IFN-β, providing new mechanisms for NS1-mediated manipulation of host immunity and BSI severity.
Optomechanical Crystals at Millikelvin Temperatures (2017)

We will present pulsed optical measurements of silicon optomechanical crystals at millikelvin temperatures. These measurements highlight the exciting new opportunities for application of microwave phononic devices in the quantum realm, but also some of the challenges.
[beta]‐arrestin 1 mediates angiotensin II induced ubiquitination and down‐regulation of TRPV4 (2009)

β‐arrestins were originally discovered to desensitize activated G protein‐coupled receptors (GPCRs), also known as seven transmembrane receptor (7TMRs). It was subsequently found that β‐arrestins also mediate 7TMR internalization by bringing the activated receptors to clathrin‐coated pits. More recently, it has been discovered that β‐arrestins can also interact with and regulate ion channels and transporters. Using a proteomic approach, we identified TRPV4 as an interacting partner of β‐arrestin 1 after stimulation of cells with angiotensin II. Here we demonstrate that β‐arrestin 1 is recruited to TRPV4 upon angiotensin II stimulation in HEK‐293 cells and vascular smooth muscle cells. Surprisingly, angiotensin II stimulation leads to ubiquitination of TRPV4 which is abolished by β‐arrestin 1 siRNA. β‐arrestin 1 shows constitutive interaction with AIP4, a known ubiquitin E3 ligase for TRPV4, which is further increased upon angiotensin stimulation. Moreover, the interaction of TRPV4 and AIP4 is also significantly reduced by β‐arrestin 1 siRNA. These findings suggest that β‐arrestin 1 serves as an adaptor for AIP4 and thereby facilitates TRPV4 ubiquitination and down‐regulation. Taken together with the previous reports of analogous function of β‐arrestins for 7TMRs, this study suggests a novel role of β‐arrestins as a general adaptor for ubiquitin E3 ligases.
Atomic Structure of Self-Pillared, Single-Unit-Cell Sn-MFI Zeolite Nanosheets (2016)

Two-dimensional MFI-type zeolites are single or near single-unit-cell thick microporous nanosheets with pore sizes of ~ 5 in diameter, formed by a network of interconnected silicon and oxygen atoms These nanosheets can be fabricated into ultra-thin membranes for the separation of isomer mixtures, such as p-xylene/o-xylene and n-butane/i-butane by allowing only the passage of isomer that fits within its micropores. In addition, application of these nanosheets can be further extended by incorporating heteroatoms, such as Sn atoms, into its framework as catalytically active sites for the isomerization of glucose to fructose, the reaction involved in production of high-fructose corn syrup. The yield of fructose during this reaction depends on the accessibility of catalytically active sites in the zeolite framework.
The mitochondrial one‑carbon metabolic pathway is associated with patient survival in pancreatic cancer (2018)

The expression levels of one-carbon metabolic enzymes were investigated and observed to be correlated with clinicopathological parameters in patients with pancreatic cancer. Mitochondrial one-carbon metabolism comprises a network of biological reactions that integrate nutrient status with nucleotide synthesis, amino acid metabolism, antioxidant reduced nicotinamide adenine dinucleotide phosphate production and epigenetic methylation processes. Previous studies have reported that the hyper-activation of mitochondrial one-carbon metabolism serves a significant role in malignant cancer phenotypes. A total of 103 patients underwent surgical resection of pancreatic ductal adenocarcinomas (PDAC) at Osaka University Hospital between April 2007 and December 2013 and were enrolled in this study. Subsequently, the expression of the one-carbon metabolic enzymes methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), aldehyde dehydrogenase 1 family member L2 (ALDH1L2), and serine hydroxymethyltransferase (SHMT2) was examined using immunohistochemical analysis. The immunohistochemical analyses demonstrated that patients with high expression levels of MTHFD2, ALDH1L2 or SHMT2 had significantly poor overall survival (OS) and disease-free survival (DFS) rates, as compared with patients with low expression levels. Furthermore, multivariate Cox proportional hazards analysis indicated that MTHFD2 and ALDH1L2 were independent prognostic factors for OS and DFS, whereas SHMT2 was not predictive of DFS. However, high and low expression levels of all three folate metabolic enzymes were significantly associated with improved OS and DFS, compared with the high expression of one or two folate metabolic enzymes. The expression levels of mitochondrial one-carbon metabolic enzymes are independent prognostic factors and potential therapeutic targets for future pancreatic cancer treatments.
FINITE ELEMENT COMPUTATION OF UNSTEADY PHASE CHANGE HEAT TRANSFER DURING FREEZING OR THAWING OF FOOD USING A COMBINED ENTHALPY AND KIRCHHOFF TRANSFORM METHOD (2001)

An improved finite element enthalpy method was developed and implemented for solving nonlinear phase changeheat transfer problems such as freezing or thawing of foods with arbitrary 3D geometries. By simultaneously applying theenthalpy and Kirchhoff transforms, all nonlinearities caused by the temperaturedependent thermophysical properties wereincorporated in a functional relationship between the volumetric specific enthalpy and the Kirchhoff function. Such a problemreformulation results in a much more convenient solution procedure and avoids the possibility of missing the apparent specificheat capacity peak and the abrupt thermal conductivity change. Algorithms for the finite element solution of the resultingtransformed equation were developed and programmed in Matlab. As the transformed equation is linear, the finite elementmatrices are constant and have to be calculated only once. This greatly improves the execution speed of the code, as comparedto traditional finite element algorithms based on the original nonlinear or enthalpytransformed Fourier equation. As aconsequence, the method is well suited for computationally intensive applications, such as numerical optimization or MonteCarlo uncertainty propagation analysis, in which typically a large number of phase change heat transfer problems must besolved. As an illustration, the freezing of a cylinder filled with tylose was investigated. A good agreement betweenmeasurements and model predictions was obtained.
Abstract 18066: Novel NLRP3 Inflammasome Inhibitor OLT1177 Reduces Infarct Size in a Mouse Model of Myocardial Ischemia Reperfusion Injury (2017)

Introduction: Activation of the NLRP3 inflammasome during acute myocardial infarction (AMI) mediates further inflammatory injury after reperfusion. Several NLRP3 inflammasome inhibitors have been s...
A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas (2016)

The prognostic impact of TERT mutations has been controversial in IDH-wild tumors, particularly in glioblastomas (GBM). The controversy may be attributable to presence of potential confounding factors such as MGMT methylation status or patients' treatment. This study aimed to evaluate the impact of TERT status on patient outcome in association with various factors in a large series of adult diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT promoter status. The combined IDH/TERT classification divided Cohort 1 into four molecular groups with distinct outcomes. The overall survival (OS) was the shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P < 0.0001). To investigate the association between TERT mutations and MGMT methylation on survival of patients with GBM, samples from a combined cohort of 453 IDH-wild-type GBM cases treated with radiation and temozolomide were analyzed. A multivariate Cox regression model revealed that the interaction between TERT and MGMT was significant for OS (P = 0.0064). Compared with TERT mutant-MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the interaction was the lowest in the TERT mutant-MGMT methylated GBM (HR, 0.266), followed by the TERT wild-type-MGMT methylated (HR, 0.317) and the TERT wild-type-MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant-MGMT unmethylated GBM have the poorest prognosis. Our findings suggest that a combination of IDH, TERT, and MGMT refines the classification of grade II-IV diffuse gliomas.
Frequency of the Cholesteryl Ester Storage Disease Common Lipa E8sjm Mutation (C.894G&gt;A) in Various Racial And Ethnic Groups (2013)

These data indicate that CESD may be underdiagnosed in the general Caucasian and Hispanic populations, which is important since clinical trials of enzyme replacement therapy for LAL deficiency are currently being developed. Moreover, future studies on CESD prevalence in African and Asian populations may require full-gene LIPA sequencing to determine heterozygote frequencies, since c.894G>A is not common in these racial groups.
MAMMALIAN OLIGOPEPTIDE TRANSPORTERS (2022)

Protein–protein interactions play an important role in normal physiological homeostasis, with aberrant interactions being integral to the pathogenesis of many diseases and disorders. Predicated on this fact, the search for peptide- and protein-based therapeutics to mitigate diseases and disorders has led to the discovery of many different therapeutic hit and lead compounds since the therapeutic utility of porcine insulin in 1922 was first realized. While the therapeutic potential is well accepted, the absorption and disposition of these agents have largely been hindered by their hydrophilic nature and size. Here, we discuss the role of peptide transporters and the routes of permeation across biological barriers that need to be considered in order for the potential of these therapeutics to be realized. In particular, emphasis is placed on the discussion of the human oligopeptide transporter isoforms (SLC15A) to provide context into potential means where investigators may enhance small molecule, peptide-based absorption and distribution during discovery and aid in translation to the clinic.
Projection images of the position‐velocity joint spin density distribution (1990)

A new concept of phase encoding called position-velocity combined oblique Fourier phase encoding is introduced. It encodes both spatial and velocity information in a single oblique direction in the position-velocity space. Using this method, two-dimensional projection images of the three-dimensional position-velocity joint spin density distribution along different directions can be obtained. These projection images can provide detailed information on the flow system under study. The imaging of the two-dimensional projection is less time consuming compared to three-dimensional Fourier flow imaging and can be easily implemented on a conventional magnetic resonance imaging scanner.
Fine structure of adrenal cortex in rats harbouring a medullary thyroid carcinoma transfected with a corticotrophin-releasing hormone cDNA expression vector (1992)

We report the light microscopic, transmission and scanning electron microscopic features of the adrenal cortices in rats bearing a medullary thyroid carcinoma cell line transfected with a corticotrophin-releasing hormone (CRH) cDNA expression vector. The animals had elevated CRH, ACTH and corticosterone blood levels, involuted thymuses and markedly enlarged adrenal glands with prominent lipid-depleted cortices and dilated congested capillaries, similar to those of animals treated with ACTH. Using electron microscopy it was found that the enlarged fasciculata and reticularis zones were composed of large, compact cells with abundant smooth endoplasmic reticulum, prominent Golgi complexes, increased number of large mitochondria with focal loss of cristae and cavitation of the internal compartments, numerous lysosomes and prominent elongated microvilli. In addition, small cytoplasmic fragments were seen within the capillary lumina; these structures resembled microvilli that were apparently detached from adrenocortical cells and entered the blood stream via discontinuous endothelium of dilated capillaries. By scanning electron microscopy it was found that the cells had bulging surfaces with scattered pits and numerous long microvilli pointing in different directions. This animal model allows analysis of the effects of protracted CRH excess resembling tumoural CRH-dependent Cushing's syndrome in human patients. Our findings call attention to the role of microvilli in adrenocortical secretion. The increased number and size of microvilli has been thought to lead to an increase in the surface area of adrenocortical cells, thereby facilitating hormone discharge. The detachment of microvilli from adrenocortical cells may represent a form of apocrine secretion and may contribute to hypercorticosteronaemia in CRH excess.
223 Study on Synchronized Vibration in Cableways Consisted of Multiple Lifts (2010)

Synchronized vibration of lifts appears in cableway structures and has the possibility to lead to a serious accident. The purpose of this study is to analyze the vibration characteristics causing the synchronization. In this study, to construct a model of the coupled vibration of a rope and lifts, the rope was divided into multiple equivalent mass and spring elements and lifts were modeled as pendulums. Numerical analysis implies that energy of the system can concentrate in one of the lifts depending on initial phase conditions of the lifts and the vibration can become large.
Label-Free Water Sensors Using Hybrid Polymer–Dielectric Mid-Infrared Optical Waveguides (2015)

A chip-scale mid-IR water sensor was developed using silicon nitride (SiN) waveguides coated with poly(glycidyl methacrylate) (PGMA). The label-free detection was conducted at λ=2.6-2.7 μm because this spectral region overlaps with the characteristic O-H stretch absorption while being transparent to PGMA and SiN. Through the design of a hybrid waveguide structure, we were able to tailor the mid-IR evanescent wave into the PGMA layer and the surrounding water and, consequently, to enhance the light-analyte interaction. A 7.6 times enhancement of sensitivity is experimentally demonstrated and explained by material integration engineering as well as waveguide mode analysis. Our sensor platform made by polymer-dielectric hybrids can be applied to other regions of the mid-IR spectrum to probe other analytes and can ultimately achieve a multispectral sensor on-a-chip.
Optically-pumped Semiconductor Disk Lasers for Second-harmonic and Sum-frequency Generation (2007)

We report on intracavity frequency-doubling and sum-frequency generation in optically-pumped semiconductor disk lasers. High power second-harmonic red emission from a GaInNAs-based disk laser and aquamarine sum-frequency emission from a dual-wavelength semiconductor disk laser were obtained.
Automated Construction of Sparse Bayesian Networks from Unstructured Probabilistic Models and Domain Information (2013)

An algorithm for automated construction of a sparse Bayesian network given an unstructured probabilistic model and causal domain information from an expert has been developed and implemented. The goal is to obtain a network that explicitly reveals as much information regarding conditional independence as possible. The network is built incrementally adding one node at a time. The expert's information and a greedy heuristic that tries to keep the number of arcs added at each step to a minimum are used to guide the search for the next node to add. The probabilistic model is a predicate that can answer queries about independencies in the domain. In practice the model can be implemented in various ways. For example, the model could be a statistical independence test operating on empirical data or a deductive prover operating on a set of independence statements about the domain.
New Hyper Duplex Stainless Steel Welding Material for Improved Weld Performance (2007)

Abstract With the development of new high performance stainless steel grades comes the need for more advanced welding materials. Investigations of welds produced using the austenitic-ferritic welding material 27.9.5L is presented. Properties of all-weld metal as well as that of butt welds of the newly developed high alloyed duplex grade UNS S32707 (PRE number 49) are given. Documentation of tube-to-tube sheet welds in tube sheets of various stainless alloys is also presented and discussed. In particular, use of this welding material for joining the grade UNS S32707 for obtaining optimum corrosion resistance is discussed. Results from the use of weld overlays of 27.9.5.L on substrate material for providing corrosion protection to e.g. tube sheets in heat exchangers are also discussed.
Enabling Technologies and Standards for Mobile Multihop Wireless Networking (2013)

Standards play an important role in the evolution of the communication market and technologies. This chapter surveys the enabling technologies and standards for mobile multihop wireless networks by considering those that have been proposed to support multihop transmission in broadband wireless access (BWA) networks. It reviews the state of the art on WLAN technologies with multihop support. The standard was shown to be versatile in adapting to different applications and use cases through its various amendments, including the following that are surveyed in the chapter: IEEE 802.11s, IEEE 802.11z, IEEE 802.11n, and IEEE 802.11p. It then reviews the most important state-of-art technologies supporting multihop communication in WPANs. The chapter focuses in particular on lowrate-WPANs (LR-WPANs), for which the ability to support multihop/mesh topologies is mostly desirable because of the very limited communication range, as compared to the coverage area required in many typical deployments, such as large-scale monitoring environments. Controlled Vocabulary Terms wireless LAN; wireless mesh networks; wireless networks
Loss of <i><scp>CDKN</scp>2A</i> expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the <scp>CDK</scp>4/6 inhibitor <scp>PD</scp>0332991 in melanoma cell lines (2014)

We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three-quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was associated with poorer melanoma-specific survival. In 47 melanoma cell lines homozygous loss, methylation or mutation of CDKN2A gene or loss of protein (p16(INK) (4A) ) predicted sensitivity to the CDK4/6 inhibitor PD0332991, while RB1 loss predicted resistance.
Excluded volume theory of rigid plates in solution using continuous orientation distributions (2000)

A new analytical theory has been developed for the thermodynamics of dilute-to-moderately concentrated solutions of rigid plates of arbitrary dimensions. The approach presented differs from most current theories by allowing for a continuous distribution of plate orientations rather than a small set of discrete orientations. With a few simple approximations, the theory is made tractable enough to allow for the straightforward determination of the thermodynamic properties. The results of the theory, which contains no adjustable parameters, are in good agreement with the results of Monte Carlo simulations of spatially sparse distributions of plates created by random sequential addition. An example set of the free energy of mixing curves and a phase diagram are also presented, and the prospects for future development of the theory are briefly discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2366–2377, 2000