gebhart/patrepeval huggingface dataset:
0200 DIRECT ACTIVATION OF G-PROTEIN-COUPLED INWARD RECTIFYING K+ CHANNELS PROMOTE SLEEP IN RODENTS (2017)

The most common type of sleep disorder is insomnia which is characterized by difficulty falling asleep and/or maintaining sleep. Chronic insomniacs respond poorly to current treatments including benzodiazepines and non-benzodiazepines. Activation of G-protein-gated inward rectifying K channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) predominantly promote non-rapid eye movement (NREM) sleep in rodents and humans. GHB especially reduces sleep fragmentation in narcoleptic patients. The present study explored the link between direct GIRK activation and sleep regulation in rodents using our potent and selective GIRK channel activator ML297. Whole-cell patch clamp recordings from hypocretin/orexin-EGFP neurons and extracellular recordings of mouse hippocampal CA1 area in mouse brain slices were made to study cellular and synaptic actions of ML297. Wake activity and locomotion were measured using the noninvasive behavior monitoring system SmartCageTM. Furthermore, wakefulness, REM and NREM sleep were determined using the electroencephalogram/electromyogram (EEG/EMG) in wild type mice (C57BL/C) implanted with electrodes. Bath-application of ML297 (5µM) hyperpolarized resting potential, decreased membrane input resistance and blocked spontaneous firing of action potentials in hypocretin/orexin neurons. These actions were reversed after prolonged washout. ML297 (5–50µM) produced no significant effects on normal synaptic activity measured by input-output of field postsynaptic excitatory potentials and an evoked single population of spikes in the hippocampal CA1 area, suggesting ML297 principally causes long-lasting postsynaptic inhibition. Using our noninvasive SmartCageTM system we observed that ML297 (30mg/kg, i.p.) caused a prolonged inhibition of wake activity and locomotion in mice. The EEG/EMG recordings confirmed that ML297 (30mg/kg, i.p.) significantly decreased wakefulness and revealed an increase in NREM sleep without affecting REM sleep in mice. The present study for the first time has demonstrated that direct action of GIRK produces similar sleep regulation to GABAB receptor-mediated modulation. Since GIRKs channels are predominantly expressed in principal excitatory neurons, inhibition of neuronal excitability and depression of the arousal system may powerfully modulate sleep. Direct GIRK activators may present an innovative approach for treatment of chronic insomnia as well as other sleep disorders. This work was supported by NIH grants: R42 HL084990, R44 AG043203, and R44 NS086343.
Optimized Near-IR Fluorescent Agents for in Vivo Imaging of Btk Expression (2015)

Bruton’s tyrosine kinase (Btk) is intricately involved in anti-apoptotic signaling pathways in cancer and in regulating innate immune response. A number of Btk inhibitors are in development for use in treating B-cell malignancies and certain immunologic diseases. To develop robust companion imaging diagnostics for in vivo use, we set out to explore the effects of red wavelength fluorochrome modifications of two highly potent irreversible Btk inhibitors, Ibrutinib and AVL-292. Surprisingly, we found that subtle chemical differences in the fluorochrome had considerable effects on target localization. Based on iterative designs, we developed a single optimized version with superb in vivo imaging characteristics enabling single cell Btk imaging in vivo. This agent (Ibrutinib-SiR-COOH) is expected to be a valuable chemical tool in deciphering Btk biology in cancer and host cells in vivo.
Balancing risk and benefit in early-stage classical Hodgkin lymphoma (2018)

With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP<sub>escalated</sub>) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [<sup>18</sup>F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP<sub>escalated</sub> improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.
HIV vaccine delayed boosting increases Env variable region 2–specific antibody effector functions (2020)

In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.
Hafnia alvei, a probable cause of diarrhea in humans (1991)

Hafnia alvei, a member of the family Enterobacteriaceae, was the only species of bacteria cultured from the stool of a 9-month-old child who was admitted with a 3-day history of watery diarrhea. The isolated strain of H. alvei failed to produce heat-labile or heat-stable enterotoxins or Shiga-like toxin I or II and did not invade HeLa cells, nor did it cause keratoconjunctivitis (determined by the Sereny test) in a guinea pig's eye. The strain, however, induced diarrhea in 8 of 12 adult rabbits with removable intestinal ties (removable intestinal tie-adult rabbit diarrhea [RITARD] assay) and in 1 of 2 orally fed animals. No diarrhea could be induced with Escherichia coli K-12 in eight RITARD assay rabbits and three orally fed rabbits, respectively. Microscopic examination of affected animals revealed moderate inflammatory cellular infiltration of the intestinal mucosa, in which bacterial attachment to the surface epithelium and loss of the microvillus border were evident in the ileum and colon. Electron microscopy demonstrated cellular modifications of the apical surface, with cupping or pedestal formation and increased terminal web density at sites of bacterial "attachment-effacement," a well-known characteristic and mechanism of diarrhea of enteropathogenic E. coli. Identical lesions were also induced by H. alvei in rabbit ileal loops, which ruled out naturally occurring rabbit enteropathogenic E. coli strains, which are known to produce similar lesions. It is concluded that at least some strains of H. alvei have the potential to cause diarrhea and that attachment-effacement is a virulence characteristic shared by bacteria other than E. coli.
Structure-Function Analysis of SH3 Domains: SH3 Binding Specificity Altered by Single Amino Acid Substitutions (1995)

SH3 domains mediate intracellular protein-protein interactions through the recognition of proline-rich sequence motifs on cellular proteins. Structural analysis of the Src SH3 domain (Src SH3) complexed with proline-rich peptide ligands revealed three binding sites involved in this interaction: two hydrophobic interactions (between aliphatic proline dipeptides in the SH3 ligand and highly conserved aromatic residues on the surface of the SH3 domain), and one salt bridge (between Asp-99 of Src and an Arg three residues upstream of the conserved Pro-X-X-Pro motif in the ligand). We examined the importance of the arginine binding site of SH3 domains by comparing the binding properties of wild-type Src SH3 and Abl SH3 with those of a Src SH3 mutant containing a mutated arginine binding site (D99N) and Abl SH3 mutant constructs engineered to contain an arginine binding site (T98D and T98D/F91Y). We found that the D99N mutation diminished binding to most Src SH3-binding proteins in whole cell extracts; however, there was only a moderate reduction in binding to a small subset of Src SH3-binding proteins (including the Src substrate p68). p68 was shown to contain two Arg-containing Asp-99-dependent binding sites and one Asp-99-independent binding site which lacks an Arg. Moreover, substitution of Asp for Thr-98 in Abl SH3 changed the binding specificity of this domain and conferred the ability to recognize Arg-containing ligands. These results indicate that Asp-99 is important for Src SH3 binding specificity and that Asp-99-dependent binding interactions play a dominant role in Src SH3 recognition of cellular binding proteins, and they suggest the existence of two Src SH3 binding mechanisms, one requiring Asp-99 and the other independent of this residue.
HP1 proteins regulate nucleolar structure and function by secluding pericentromeric constitutive heterochromatin (2022)

Nucleoli are nuclear compartments regulating ribosome biogenesis and cell growth. In embryonic stem cells (ESCs), nucleoli containing transcriptionally active ribosomal genes are spatially separated from pericentromeric satellite repeat sequences packaged in largely repressed constitutive heterochromatin (PCH). To date, mechanisms underlying such nuclear partitioning and the physiological relevance thereof are unknown. Here we show that repressive chromatin at PCH ensures structural integrity and function of nucleoli during cell cycle progression. Loss of heterochromatin proteins HP1α and HP1β causes deformation of PCH, with reduced H3K9 trimethylation (H3K9me3) and HP1γ levels, absence of H4K20me3 and upregulated major satellites expression. Spatially, derepressed PCH aberrantly associates with nucleoli accumulating severe morphological defects during S/G2 cell cycle progression. Hp1α/β deficiency reduces cell proliferation, ribosomal RNA biosynthesis and mobility of Nucleophosmin, a major nucleolar component. Nucleolar integrity and function require HP1α/β proteins to be recruited to H3K9me3-marked PCH and their ability to dimerize. Correspondingly, ESCs deficient for both Suv39h1/2 H3K9 HMTs display similar nucleolar defects. In contrast, Suv4-20h1/2 mutant ESCs lacking H4K20me3 at PCH do not. Suv39h1/2 and Hp1α/β deficiency-induced nucleolar defects are reminiscent of those defining human ribosomopathy disorders. Our results reveal a novel role for SUV39H/HP1-marked repressive constitutive heterochromatin in regulating integrity, function and physiology of nucleoli.
Hematologic Genetic Testing in High-risk Patients Before Knee Arthroplasty: A Pilot Study (2010)

Level IV, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
Utility of optical heterodyne displacement sensing and laser ultrasonics as in situ process control diagnostic for additive manufacturing (2018)

An in situ process control monitor is presented by way of experimental results and simulations, which utilizes a pulsed laser ultrasonic source as a probe and an optical heterodyne displacement meter as a sensor. The intent is for a process control system that operates in near real time, is nonintrusive, and in situ: A necessary requirement for a serial manufacturing technology such as additive manufacturing (AM). We show that the diagnostic approach has utility in characterizing the local temperature, the area of the heat-affected zone, and the surface roughness (Ra ∼ 0.4 μm). We further demonstrate that it can be used to identify solitary defects (i.e., holes) on the order of 10 to 20 μm in diameter. Moreover, the technique shows promise in measuring properties of materials with features that have a small radius of curvature. We present results for a thin wire of ∼650 μm in diameter. By applying multiple pairs of probe–sensor systems, the diagnostic could also measure the local cooling rate on the scale of 1 μs. Finally, while an obvious application is used in AM technology, then all optical diagnostics could be applied to other manufacturing technologies.
Thermo-mechanical design of a generic 0-level MEMS package using chip capping and Through Silicon Via's (2010)

This paper describes the thermo-mechanical design of an advanced zero-level capping technology used for packaging of a MEMS die. The package approach uses Intermetallic Compound (IMC) bonding to seal the MEMS die with a cap, and uses Through Silicon Via's (TSV) to provide the electrical connections from the MEMS die to the second level substrate (LTCC or PCB). Advanced FEM based thermo-mechanical simulations are performed to estimate the impact of processing and temperature cycling on the mechanical stresses and deformations induced in the structure. Special focus goes to the rigid CuSn IMC bond, the copper TSV using a polymer dielectric and the cap deflection under a pressure of 1 bar (vacuum inside) and 90 bar (simulating overmoulding). Finally, the impact of assembling the MEMS package on an LTCC substrate and an FR4 printed circuit board with CuSn, respectively solder connections is investigated with respect to the package reliability, the cap deflection and the strain and anchor rotation at location of the MEMS.
Analogues of Orphan Nuclear Receptor Small Heterodimer Partner Ligand and Apoptosis Inducer (E)-4-[3-(1-Adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic Acid. 2. Impact of 3-Chloro Group Replacement on Inhibition of Proliferation and Induction of Apoptosis of Leukemia and Cancer Cell Lines (2011)

The parent phenol of adapalene and its (E)-cinnamic acid analogue were found to induce cancer cell apoptosis but cause adverse systemic effects when administered to mice. In contrast, their respective 5-Cl- and 3-Cl-substituted analogues had their adverse effects mitigated without a comparable loss of cancer cell inhibitory activity. As a result, pharmacologic space in this region of the cinnamic phenyl ring scaffold was explored. Various substituents were introduced, and their effects on cancer cell proliferation and viability were evaluated. Cinnamic acids having 3-Br, CN, NO(2), NH(2), OMe, and N(3) groups had activity comparable to that of 4-[3'-(1-adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic acid. A comparative molecular field analysis study indicated that introduction of an H-bond acceptor at position 3 of the central phenyl ring would favor inhibition of leukemia cell viability, and docking suggested its hydrogen bonding with a polar group in a small heterodimer partner homology model. The 3-CN, NO(2), NH(2), and OH analogues also inhibited MMTV-Wnt1 murine mammary stem cell viability.
MP92-01 PD-1 EXPRESSION ON CLASSICAL MONOCYTES (CM) IS AN INDEPENDENT PREDICTOR OF CANCER SPECIFIC SURVIVAL IN CLEAR CELL RENAL CARCINOMA (CCRCC) (2016)

genetic counseling, Klinefelter syndrome (3.6%) who underwent testicular sperm extraction (no men with Klinefelter syndrome had a positive YCM assay), and men with chromosomal abnormalities of the Y chromosome (1.9%) who chose donor sperm or adoption. Sequential testing for karyotype first and then YCM, results in 9.8% of men savings of $500. This reduces the average cost of testing to $1,250.69 per patient, a savings of 3.8%.
Liquid Microjunction Surface Sampling Probe Fluid Dynamics: Computational and Experimental Analysis of Coaxial Intercapillary Positioning Effects on Sample Manipulation (2011)

A coaxial geometry liquid microjunction surface sampling probe (LMJ-SSP) enables direct extraction of analytes from surfaces for subsequent analysis by techniques like mass spectrometry. Solution dynamics at the probe-to-sample surface interface in the LMJ-SSP has been suspected to influence sampling efficiency and dispersion but has not been rigorously investigated. The effect on flow dynamics and analyte transport to the mass spectrometer caused by coaxial retraction of the inner and outer capillaries from each other and the surface during sampling with a LMJ-SSP was investigated using computational fluid dynamics and experimentation. A transparent LMJ-SSP was constructed to provide the means for visual observation of the dynamics of the surface sampling process. Visual observation, computational fluid dynamics (CFD) analysis, and experimental results revealed that inner capillary axial retraction from the flush position relative to the outer capillary transitioned the probe from a continuous sampling and injection mode through an intermediate regime to sample plug formation mode caused by eddy currents at the sampling end of the probe. The potential for analytical implementation of these newly discovered probe operational modes is discussed.
Effective utilization of acoustic wave sensor responses: simultaneous measurement of velocity and attenuation (2003)

When using acoustic wave devices as sensors, responses arise from perturbations in wave-propagation characteristics (velocity and attenuation) caused by wave interactions with a surface layer. Simultaneous measurement of both velocity and attenuation changes helps elucidate the wave-perturbation mechanisms. A number of wave-surface-layer interactions have been investigated involving surface acoustic waves (SAWs) in the gas phase and acoustic plate modes (APMs) in liquids. These include mass loading of a SAW, acoustoelectric interactions between SAWs and a conductive film overlay, mass loading of an APM, and viscous coupling of an APM to an adjacent liquid medium.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A multi-MAC approach to overcome the throughput limits of 802.11 WLANs (2004)

In this paper, we explore MAC approaches that could provide increased throughput to 802.11 WLANs. First we analyze the throughput performance of 802.11 WLANs by deriving expressions for the maximum achievable throughput. Based on these results, we identify the main throughput-limiting factors and discuss approaches that may reduce their impact. We also propose a novel approach, called multiMAC, which allows a significant throughput increase without the need for new high-rate transmission modes. An important feature of our approach is its interoperability and compatibility with current 802.11 WLANs. Furthermore it is very simple, requires no hardware support, and can easily be implemented in software.
Correction: Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study (2019)

[This corrects the article DOI: 10.1371/journal.pone.0164646.].
Ru-Loaded C12A7:e– Electride as a Catalyst for Ammonia Synthesis (2017)

The artificial mass production of ammonia has supported the increase in human population and modern civilization for over 100 years. However, more efficient ammonia production is now a significant concern for society. Here we show that Ru-loaded C12A7:e– electride derived from 12CaO·7Al2O3 (C12A7:O2–) acts as an efficient and stable catalyst for ammonia synthesis. Ammonia synthesis over Ru nanoparticles-loaded C12A7:e– (Ru/C12A7:e–) is distinct from other conventional catalysts in both mechanism and properties. The dissociative adsorption of N2 molecules, which is the largest energy barrier in ammonia synthesis for conventional catalysts, is no longer the rate-limiting step for the Ru/C12A7:e– catalyst. In addition, Ru on the electride prevents the inhibition of ammonia synthesis by hydrogen adatoms, known as hydrogen poisoning, which is a common and serious drawback of Ru catalysts. This characteristic results in the highly efficient formation of ammonia over the Ru/C12A7:e– catalyst.
Mutation in theSLC4A11Gene Associated with Autosomal Recessive Congenital Hereditary Endothelial Dystrophy in a Large Saudi Family (2008)

A novel SLC4A11 mutation (Thr271Met) is associated with autosomal recessive CHED in a pedigree from the Kingdom of Saudi Arabia and provides additional support that mutations in this gene cause disease.
Cytokines and Infection in Patients with Cirrhosis (1994)

Journal Article Cytokines and Infection in Patients with Cirrhosis Get access Baudouin Byl, Baudouin Byl Infectious Diseases Clinic and Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium Reprints or correspondence: Dr. B. Byl, Infectious Diseases Clinic, Erasme Hospital, Route de Lennik 808, 1070 Bruxelles, Belgium. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jacques Devière Jacques Devière Infectious Diseases Clinic and Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 18, Issue 6, June 1994, Pages 1015–1016, https://doi.org/10.1093/clinids/18.6.1015-a Published: 01 June 1994