gebhart/patrepeval huggingface dataset:
Ligands Raise the Constraint That Limits Constitutive Activation in G Protein-coupled Opioid Receptors (2013)

Using a cell-free bioluminescence resonance energy transfer strategy we compared the levels of spontaneous and ligand-induced receptor-G protein coupling in δ (DOP) and μ (MOP) opioid receptors. In this assay GDP can suppress spontaneous coupling, thus allowing its quantification. The level of constitutive activity was 4-5 times greater at the DOP than at the MOP receptor. A series of opioid analogues with a common peptidomimetic scaffold displayed remarkable inversions of efficacy in the two receptors. Agonists that enhanced coupling above the low intrinsic level of the MOP receptor were inverse agonists in reducing the greater level of constitutive coupling of the DOP receptor. Yet the intrinsic activities of such ligands are identical when scaled over the GDP base line of both receptors. This pattern is in conflict with the predictions of the ternary complex model and the "two state" extensions. According to this theory, the order of spontaneous and ligand-induced coupling cannot be reversed if a shift of the equilibrium between active and inactive forms raises constitutive activation in one receptor type. We propose that constitutive activation results from a lessened intrinsic barrier that restrains spontaneous coupling. Any ligand, regardless of its efficacy, must enhance this constraint to stabilize the ligand-bound complexed form.
Angiotensin II formation by chymase in the cardiovascular tissue. (1998)

Angiotensin-converting enzyme (ACE) inhibitors attenuated the contractile responses to angiotensin (Ang) I of arterial strips of humans, monkeys, and dogs, as can be expected. Unexpectedly, however, the response was not abolished by sufficient doses of ACE inhibitors, the facts suggesting the Ang I conversion by a non-ACE enzyme(s). HPLC analysis of the incubation product of Ang I with vascular tissues revealed that Ang II was yet formed despite complete ACE inhibition, and the ACE inhibitor-insensitive Ang II formation was blocked by chymostatin. The disclosed Ang II-forming enzyme was identified as chymase, which was later found in abundance in the human heart. Another notable discovery by us is the species difference in chymase processing of Ang I: chymases of primates, dog, and hamster convert Ang I to Ang II, while chymases of rat, rabbit, and probably mouse do not. Accumulating evidence indicating that Ang II is not merely a vasopressor agent but also a growth-promoting factor, which leads to tissue hypertrophy and fibrosis, together with the results our studies lead us to propose the tissue-remodeling roles of chymase-formed Ang II in various cardiovascular diseases: dog neointimal proliferation after angioplasty, hamster cardiomyopathy, etc., in which chymase mRNA is increased concordantly with tissue remodeling. The fact that Ang II receptor antagonists, not ACE inhibitors, suppress the tissue remodeling supports our argument that Ang II is formed predominantly by chymase in diseased tissues. Orally active chymase inhibitors, evolving in our study, should help explore the actual roles of chymase as well as the rational treatment of tissue-remodeling disorders.
The Genetic, Developmental, and Molecular Bases of Fruit Size and Shape Variation in Tomato (2004)

Fruit, corresponding to the plant's ovary (or ovaries), protect seed development and serve as the vehicle for seed dispersal to different habitats for species propagation. Fruit also provide humans with a source of nutrition, culinary diversity, and often great pleasure. Humans consume fruit from a
Low-complexity turbo equalization for single-carrier systems without cyclic prefix (2008)

In this paper, we present a low complexity frequency-domain turbo equalization algorithm for single-carrier system without cyclic prefix. Comparing with the traditional time-domain turbo equalization, the proposed algorithm can be implemented in the frequency domain with fast Fourier transform (FFT), and it does not involve matrix inversion. Simulation results show that the proposed algorithm also exhibits good performance.
3D Simulation of Doping Fluctuation Effects in Trigate FETs (2007)

Abstract: In this paper, we investigate random doping fluctuation effects in Trigate SOI MOSFETs by solving the 3D Poisson, Drift-Diffusion and Continuity equations numerically. The presence of a single doping impurity atom induces a threshold voltage (VTH) shift in the transistor. The threshold shift depends on the polarity and the physical location of the impurity atom. Our results show the typical variation of VTH per doping atom is a few tens of mV. The variation of VTH is greater for an inversion-mode (IM) transistor than for an accumulation-mode (AM) device.
Pathogenesis of porcine Actinobacillus pleuropneumonia, part II: roles of proinflammatory cytokines. (1999)

The in vitro production of proinflammatory cytokines after stimulation with Actinobacillus pleuropneumoniae and the relation of these cytokines in vivo with the disease caused by A. pleuropneumoniae were investigated. Within 24 h, in vitro stimulation by A. pleuropneumoniae (serotype 1) preparations, including killed bacteria, bacterial culture supernatant, lipopolysaccharide, and bacterial extracts, porcine pulmonary alveolar macrophages (PAM) produced significant (P < 0.05) amounts of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) as measured by bioassays. The supernatants containing interleukin-8 from PAM after stimulation by bacterial preparations showed significant neutrophil chemotaxis, while bacterial preparations alone did not. After in vivo infection with A. pleuropneumoniae, the mean levels of TNF-alpha and IL-1 in serum, as measured by bioassays, were elevated 37- to 27836-fold for TNF-alpha and 11- to 5941-fold higher for IL-1 within 4 d post-infection, depending on the treatments, and remained elevated up to Day 7. Both cytokines were also detected in porcine lungs by bioassays and immunocytochemistry. The results indicated that both secreted and surface components of A. pleuropneumoniae can stimulate PAM to produce proinflammatory mediators. Neutrophil chemoattractants rather than bacterial components are the major factor causing acute lung inflammation. The elevation of TNF-alpha and IL-1 in pigs occurred coincident with the onset of acute clinical disease.
Influence of harmonic distortions of driving signal on the measurement of Mach-Zehnder modulator parameters (2014)

In this paper, we describe the influence of harmonic distortions of RF driving signal on the measurement of Mach-Zehnder modulator parameters, those are half-wave voltage and intrinsic chirp parameter. The influences on the measured parameters were experimentally verified in the presence of 2nd and 3rd order harmonic distortions individually.
Predicting Sustained Clinical Response to Rituximab in Moderate to Severe Systemic Manifestations of Primary Sjögren Syndrome (2022)

Our data suggest that patients with pSS should be co-prescribed immunosuppressant with rituximab, and treatment should aim to achieve complete depletion. About one in six patients develop 2NDNR in repeat cycles. Humanized or type 2 anti-CD20 antibodies may improve clinical response in extra-glandular pSS.
10−20 Level of Accuracy for Optical Frequency Ratio Measurements (2019)

Optical frequency combs give access to the fast oscillation of optical clocks' transitions, nowadays reaching 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-17</sup> /√τ level of stability [1] and 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-18</sup> level of accuracy [2]-[4]. Besides allowing a phase-coherent down-conversion to the electronically accessible radio frequencies for generating a time scale, they represent a gear in the optical domain enabling comparisons between optical frequency standards based on different atomic species [5]. Due to the need of high signal-to-noise ratio of the optical beat notes between the clocks' local oscillators and the frequency comb teeth, dedicated non-linear amplifiers with subsequent frequency conversion to the spectral region of interest is desired. Such approach allows to speed up measurement time for performing clocks' inter-comparisons and increase the robustness of the experimental setup.
Figure S4 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy (2023)

&lt;p&gt;Supplementary Figure 4: Weak correlation of TE expression induction with DNA methylation change and viral mimicry activation.&lt;/p&gt;
Structural biology of presenilin 1 complexes (2014)

The presenilin genes were first identified as the site of missense mutations causing early onset autosomal dominant familial Alzheimer's disease. Subsequent work has shown that the presenilin proteins are the catalytic subunits of a hetero-tetrameric complex containing APH1, nicastrin and PEN-2. This complex (variously termed presenilin complex or gamma-secretase complex) performs an unusual type of proteolysis in which the transmembrane domains of Type I proteins are cleaved within the hydrophobic compartment of the membrane. This review describes some of the molecular and structural biology of this unusual enzyme complex. The presenilin complex is a bilobed structure. The head domain contains the ectodomain of nicastrin. The base domain contains a central cavity with a lateral cleft that likely provides the route for access of the substrate to the catalytic cavity within the centre of the base domain. There are reciprocal allosteric interactions between various sites in the complex that affect its function. For instance, binding of Compound E, a peptidomimetic inhibitor to the PS1 N-terminus, induces significant conformational changes that reduces substrate binding at the initial substrate docking site, and thus inhibits substrate cleavage. However, there is a reciprocal allosteric interaction between these sites such that prior binding of the substrate to the initial docking site paradoxically increases the binding of the Compound E peptidomimetic inhibitor. Such reciprocal interactions are likely to form the basis of a gating mechanism that underlies access of substrate to the catalytic site. An increasingly detailed understanding of the structural biology of the presenilin complex is an essential step towards rational design of substrate- and/or cleavage site-specific modulators of presenilin complex function.
Correction: Antibody Responses against Xenotropic Murine Leukemia Virus-Related Virus Envelope in a Murine Model (2011)

Background: Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC). Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/ prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV.
Symbol time offset estimation in coherent OFDM systems (2002)

This paper presents a symbol time offset estimator for coherent orthogonal frequency division multiplexing (OFDM) systems. The estimator exploits both the redundancy in the cyclic prefix and available pilot symbols used for channel estimation. The estimator is robust against frequency offsets and is suitable for use in dispersive channels. We base the estimator on the maximum-likelihood estimator for the additive white Gaussian noise channel. Simulations for an example system indicate a system performance as close as 0.6 dB to a perfectly synchronized system.
Data from Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients (2023)

&lt;div&gt;Abstract&lt;p&gt;Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. &lt;i&gt;Pexa-Vec&lt;/i&gt; (&lt;i&gt;Pexastimogene Devacirepvec&lt;/i&gt;; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of &lt;i&gt;Pexa-Vec&lt;/i&gt; ahead of planned surgical resection of the metastases. Grade 3 and 4 &lt;i&gt;Pexa-Vec–&lt;/i&gt;associated side effects were lymphopaenia and neutropaenia. &lt;i&gt;Pexa-Vec&lt;/i&gt; was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, &lt;i&gt;Pexa-Vec&lt;/i&gt; was found in the majority of analyzed tumors. &lt;i&gt;Pexa-Vec&lt;/i&gt; therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.&lt;/p&gt;&lt;/div&gt;
Supplementary Methods, Legends for Figures 1-3, Videos 1-4 from p38γ Promotes Breast Cancer Cell Motility and Metastasis through Regulation of RhoC GTPase, Cytoskeletal Architecture, and a Novel Leading Edge Behavior (2023)

&lt;p&gt;PDF file - 193K&lt;/p&gt;
Superior Rechargeability and Efficiency of Lithium–Oxygen Batteries: Hierarchical Air Electrode Architecture Combined with a Soluble Catalyst (2014)

Abstract The lithium–oxygen battery has the potential to deliver extremely high energy densities; however, the practical use of Li‐O 2 batteries has been restricted because of their poor cyclability and low energy efficiency. In this work, we report a novel Li‐O 2 battery with high reversibility and good energy efficiency using a soluble catalyst combined with a hierarchical nanoporous air electrode. Through the porous three‐dimensional network of the air electrode, not only lithium ions and oxygen but also soluble catalysts can be rapidly transported, enabling ultra‐efficient electrode reactions and significantly enhanced catalytic activity. The novel Li‐O 2 battery, combining an ideal air electrode and a soluble catalyst, can deliver a high reversible capacity (1000 mAh g −1 ) up to 900 cycles with reduced polarization (about 0.25 V).
SPUR: A VLSI Multiprocessor Workstation (1985)

SPUR (Symbolic Processing Using RISCs) is a workstation for conducting parallel processing research. SPUR contains 6 to 12 high-performance homogeneous processors connected with a shared bus. The number of processors is large enough to permit parallel processing experiments, but small enough to allow packaging as a personal workstation. The restricted processor count also allows us to build powerful RISC processors, which include support for Lisp and IEEE floating-point, at reasonable cost. This paper presents a specification of SPUR and the results of some early architectural experiments. SPUR features include a large virtually-tagged cache, address translation without a translation buffer, LISP support with datatype tags but without microcode, multiple cache consistency in hardware, and an IEEE floating-point coprocessor without microcode
Neutron Propagation from a Pulsed Reactor (2024)

Neutron pulse propagation in thermal columns of a pulsed Triga-type reactor are investigated experimentally. The results are compared with the predictions of a Green's method calculation using a time-dependent diffusion kernel.
A survey on vehicle-to-vehicle propagation channels (2009)

Traffic telematics applications are currently under intense research and development for making transportation safer, more efficient, and more environmentally friendly. Reliable traffic telematics applications and services require vehicle-to-vehicle wireless communications that can provide robust connectivity, typically at data rates between 1 and 10 Mb/s. The development of such VTV communications systems and standards require, in turn, accurate models for the VTV propagation channel. A key characteristic of VTV channels is their temporal variability and inherent non-stationarity, which has major impact on data packet transmission reliability and latency. This article provides an overview of existing VTV channel measurement campaigns in a variety of important environments, and the channel characteristics (such as delay spreads and Doppler spreads) therein. We also describe the most commonly used channel modeling approaches for VTV channels: statistical as well as geometry-based channel models have been developed based on measurements and intuitive insights. Extensive references are provided.
Role of the Glucagon Receptor COOH-Terminal Domain in Glucagon-Mediated Signaling and Receptor Internalization (1997)

The binding of glucagon to its hepatic receptor is known to result in a number of effects, including the intracellular accumulation of cAMP, the mobilization of intracellular Ca2+, and the endocytosis of glucagon and its receptor into intracellular vesicles. In this study, we begin to define the functional role of the COOH-terminal tail of the human glucagon receptor in glucagon-stimulated signal transduction and receptor internalization. We have created and expressed in Chinese hamster ovary (CHO) cells five truncation mutants in which the COOH-terminal 24, 56, 62, 67, and 73 amino acids have been removed. Cells expressing relevant truncated receptors were assayed for cell surface expression by immunofluorescence, for ligand-binding properties, for cAMP and Ca2+-mediated signal transduction properties, and for receptor endocytosis. In addition, a mutant receptor containing seven serine-to-alanine mutations in the COOH-terminal tail was studied. Our results reveal the following: 1) a region of the COOH-terminal tail that is required for proper cell surface expression, 2) the COOH-terminal 62 amino acids, which comprise the majority of the tail, are not required for ligand binding, cAMP accumulation, or Ca2+ mobilization, and 3) phosphorylation of the COOH-terminal tail is crucial for glucagon-stimulated receptor endocytosis.
Innovative power generators for energy harvesting using electroactive polymer artificial muscles (2008)

The type of electroactive polymer known as dielectric elastomers has shown considerable promise for a variety of actuator applications and may be well suited for harvesting energy from environmental sources such as ocean waves or water currents. The high energy density and conversion efficiency of dielectric elastomers can allow for very simple and robust "direct drive" generators. Preliminary energy harvesting generators based on dielectric elastomers have been tested. A generator attached to a rotating waterwheel via a crankshaft produced 35 mJ per revolution in a laboratory test with an actual water flow. A generator that harvests the energy of ocean waves for purposes of supplying power to ocean buoys (such as navigation buoys) was tested at sea for two weeks. This buoy-mounted generator uses a proof-mass to provide the mechanical forces that stretch and contract the dielectric elastomer generator. The generator operated successfully during the sea trials. Wave conditions were very small during this test. Although the device did not produce large amounts of power, it did produce net power output with waves as small as 10 cm peak-to-peak wave height. Both the waterwheel and buoy-mounted generators will be scaled up to produce larger amounts of power. The use of significantly larger amounts of dielectric elastomer material to produce generator modules with outputs in the kilowatt range is being investigated for application to ocean wave power systems.
Synergy between In situ Cryoablation and TLR9 Stimulation Results in a Highly Effective In vivo Dendritic Cell Vaccine (2006)

Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumor antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We have previously shown that in situ tumor destruction by ablative treatments efficiently delivers antigens for the in vivo induction of antitumor immunity. In this article, we show that although 20% of the draining lymph node DCs acquire intratumorally injected model antigens after in situ cryoablation, only partial protection against a subsequent tumor rechallenge is observed. However, we also show that a combination treatment of cryoablation plus TLR9 stimulation via CpG-oligodeoxynucleotides is far more effective in the eradication of local and systemic tumors than either treatment modality alone. Analysis of the underlying mechanism revealed that in situ tumor ablation synergizes with TLR9 stimulation to induce DC maturation and efficient cross-presentation in tumor-bearing mice, leading to superior DC function in vivo. Therefore, in situ tumor destruction in combination with CpG-oligodeoxynucleotide administration creates a unique "in situ DC vaccine" that is readily applicable in the clinic.
Polymer-bound protoheme–mono-N-[3-(imidazol-1-yl)propyl]amide and –mono-N-[5-(2-methylimidazol-1-yl)pentyl]amide (1982)

Poly(1-vinyl-2-pyrrolidone)-bound protoheme–mono-N-[3-(imidazol-1-yl)propyl]amide and –mono-N-[5-(2-methylimidazol-1-yl)pentyl]amide from oxygen adducts with life time of ca. 1 h in an aqueous medium cooled to –30 °C, but non-bound protoheme analogues do not form under the same conditions.
A FinnGen pilot clinical recall study for Alzheimer’s disease (2023)

Successful development of novel therapies requires that clinical trials are conducted in patient cohorts with the highest benefit-to-risk ratio. Population-based biobanks with comprehensive health and genetic data from large numbers of individuals hold promise to facilitate identification of trial participants, particularly when interventions need to start while symptoms are still mild, such as for Alzheimer's disease (AD). This study describes a process for clinical recall studies from FinnGen. We demonstrate the feasibility to systematically ascertain customized clinical data from FinnGen participants with ICD10 diagnosis of AD or mild cognitive disorder (MCD) in a single-center cross-sectional study testing blood-based biomarkers and cognitive functioning in-person, computer-based and remote. As a result, 19% (27/140) of a pre-specified FinnGen subcohort were successfully recalled and completed the study. Hospital records largely validated registry entries. For 8/12 MCD patients, other reasons than AD were identified as underlying diagnosis. Cognitive measures correlated across platforms, with highest consistencies for dementia screening (r = 0.818) and semantic fluency (r = 0.764), respectively, for in-person versus telephone-administered tests. Glial fibrillary acidic protein (GFAP) (p < 0.002) and phosphorylated-tau 181 (pTau-181) (p < 0.020) most reliably differentiated AD from MCD participants. We conclude that informative, customized clinical recall studies from FinnGen are feasible.