gebhart/patrepeval huggingface dataset:
Plasticity of adipose tissue: a promising therapeutic avenue in the treatment of cardiovascular and blood diseases? (2005)

The adipose tissue represents a large amount of adult tissues. For long time, it was considered as a poorly active overgrown and undesirable tissue even if its usefulness was demonstrated in reconstructive surgery. It was studied for its main involvement in energy metabolism and disorders as diabetes and obesity. More recently, its endocrine functions emerged and appeared to play a key role in many physiological situations such as inflammation and immunity. The presence of preadipocytes throughout life was demonstrated using primary culture technology from cells derived from adipose tissue. These cells can display a macrophagic or endothelial potential according to their environment and could be now considered as vascular progenitors. Differentiation of various adipose derived cell subsets towards functional cardiomyocytes, osteoblasts, haematopoietic and neural cells was also obtained in vitro. Altogether, these data emphasise the need to consider with a new look preadipocyte status and adipose tissue biology. These spectacular data, together with the fact that adipose tissue is easy to obtain lead to numerous and promising perspectives in regenerative medicine. They highlight the concept that progenitor cells from adipose tissue constitute an alternative for cells-based strategies designed for the treatment of cardiovascular diseases.
CYP3A4 phenotyping with midazolam to predict sunitinib exposure. (2013)

2592 Background: Patients treated with sunitinib show high inter-patient variability in drug exposure (40-60%), which is largely unexplained. Since sunitinib is metabolized by CYP3A4, variability in the activity of this enzyme may explain a considerable proportion of the observed variability. We therefore prospectively studied the relationship between CYP3A4 activity and systemic exposure to sunitinib. Methods: In fifteen patients treated with sunitinib in a four weeks “on” – two weeks “off” regimen the pharmacokinetics of sunitinib and its active metabolite SU12662 were assessed. To determine sunitinib+SU12662 steady-state exposure, samples were collected over 24hrs after at least 14 days of sunitinib therapy. To assess CYP3A4 activity, midazolam 7.5mg orally was administered on the final day of the two weeks “off”. Plasma concentrations were measured over a period of 7hrs to determine midazolam exposure. Exposures (AUC) were calculated using a trapezoidal approach (Phoenix WinNonlin v6.3). The relationship between CYP3A4 activity (midazolam exposure) and sunitinib+SU12662 exposure was determined by linear regression analysis. The percentage of variability in sunitinib+SU12662 exposure that could be explained by CYP3A4 activity was calculated by Pearson’s correlation. In addition, the correlation between sunitinib+SU12662 C trough levels and sunitinib+SU12662 exposure was assessed. Results: A strong correlation between midazolam exposure (AUC 0-7hr ) and steady-state sunitinib+SU12662 exposure (AUC 0-24hr ) was found (p= 0.002); CYP3A4 activity explained 55% of the observed inter-patient PK variability of sunitinib+SU12662. Furthermore sunitinib+SU12662 C trough levels were highly predictive (96%) for overall sunitinib+SU12662 exposure (AUC 0-24hr ). Conclusions: Midazolam as a phenotyping probe could be useful before start of sunitinib therapy to identify patients at risk for under- respectively overtreatment at a standard dosage regimen. Therefore, CYP3A4 phenotyping could be useful to individualize sunitinib therapy. Additionally, sunitinib+SU12662 trough levels are highly predictive for sunitinib+SU12662 exposure and thus can be used for monitoring and guiding sunitinib therapy in clinical practice. Clinical trial information: NCT01743300.
Colloids (2002)

Abstract This article describes mono‐ and bimetallic colloid catalysts with regard to their wet chemical preparation and to selected applications in organic synthesis — namely of fine chemicals — and in fuel cells. The development of the field is covered from Faraday's first experiment in 1857 to recent papers published in 2002.
Impact of Gut Microbiota on Host Glycemic Control (2019)

Given that obesity and associated disorder type II diabetes mellitus have reached epidemic proportions worldwide, the development of efficient prevention and therapeutic interventions is a global public health interest. There is now a large body of evidence suggesting that the micro-organisms colonizing the human gut, known as gut microbiota, play a central role in human physiology and metabolism. Understanding how gut microbiota affects and regulates key metabolic functions such as glucose regulation and insulin resistance is an important health issue. The present review summarizes recent advances in our understanding of how gut bacterial species interfere with host metabolic phenotype. We will examine key biological molecular mechanisms underlying the impact of gut microbiota on host glycemic control including: incretin secretion, short-chain fatty acid production, bile acid metabolism, and adipose tissue regulation. We will highlight how prebiotic/probiotic interventions affect these bacterial processes and are now considered as promising approaches to treat obese and diabetic patients.
Predictors of radiation sensitivity and resistance (2007)

Local control of tumor is a very important predictor of outcome in all cancer patients, including quality of life and survival. Local tumor failure is the cause of 40-60% of cancer deaths, and may occur in 60-80% of cancer patients at the time of death. Any process that enhances tumor cell kill for a given radiation dose (sensitization) is important, and investigators have focused on three tumor parameters that are likely to influence local tumor control after radiotherapy: intrinsic radiosensitivity, the degree of tumor hypoxia, and the rate of repopulation of tumor cells. In this chapter, we will discuss these three parameters as well as modifiers of radiation effects. Any factor that decreases the relative amount of normal tissue injury is also important and can affect the therapeutic benefit of treatment. We will discuss these factors as well (Figure 17.1).
Characterizing the Tautomers of Protonated Aniline Using Differential Mobility Spectrometry and Mass Spectrometry (2017)

The site of protonation for gas-phase aniline has been debated for many years, with many research groups contributing experimental and computational evidence for either the amino-protonated or the para-carbon-protonated tautomer as the gas-phase global minimum structure. Here, we employ differential mobility spectrometry (DMS) and mass spectrometry (MS) to separate and characterize the amino-protonated (N-protonated) and para-carbon-protonated ( p-protonated) tautomers of aniline. We demonstrate that upon electrospray ionization (ESI), aniline is protonated predominantly at the amino position. Similar analyses are conducted on another three isotopically labeled forms of aniline to confirm our structural assignments. We observe a significant reduction of the relative population of the p-protonated tautomer when a protic ESI solvent is employed (methanol/water) compared to when an aprotic solvent (acetonitrile) is employed. We also observe conversion of the p-protonated species into the N-protonated species upon clustering with protic solvent vapor post-DMS selection-a finding supported by previous experimental data acquired using DMS-MS.
Latency and Power Measurements on a 64-kb Hybrid Josephson-CMOS Memory (2007)

A 64-kbit sub-nanosecond Josephson-CMOS hybrid RAM memory is being developed with hybrid high-speed interface circuits. The hybrid memory is designed and fabricated using a commercially available 0.18 mum CMOS process and NEC-SRL's 2.5 kA/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> Nb process for Josephson junctions. The memory bit-line output signals are detected by ultra-low power, high-speed Josephson devices. The most challenging part of the memory system is the input amplifier; the performance of this amplifier is optimized by minimizing its parasitic capacitance loading. Functionality tests were reported at the ASC 2004, high-speed measurements are the focus of this paper. Most of the power dissipation in the memory system occurs in the input interface circuits. The power dissipation and delay for the interface circuit are reported. The delay time and power dissipation of the CMOS part (including drivers, decoders, and cells), which contributes most to the total access time of the hybrid memory, are measured. The relation of measurements to simulations will be presented. Plans for future designs to reduce power dissipation and latency are described.
Explanation based on contexts (2003)

The authors present a hypertext-based explanation mechanism built on an existing diagnostic expert system. The system is a decision support tool for experts analyzing the condition of rotating machinery. Explanation for the system is based on context. It guides interaction and search for suitable explanations. Questions and answers are modeled separately, allowing heuristic answering. System knowledge is modeled as explicable objects to make explanations more modular. Using context to maintain a dialogue is discussed with an implementational view, and explanation techniques of an actual real-world system are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
ChemInform Abstract: Enantioselective Conjugate Additions (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Fixed Position Control of Underwater Vehicle (2016)

Studies on the underwater vehicle: UWV are classified into automatic control called AUVs and wired control type: ROVs. Generally driving force of the UWV is employed a screw or a water jet. Most of UWV studies have been focused on attitude control systems. However few researches attempted position control systems. Since viscosity of water is higher than the ground of viscosity, the UWV is strongly influenced by disturbances such as wave. It is difficult to stay at the constant position. The purpose of our research, therefore, is to propose fixed position control for the UWV. In this paper, a novel control system for the position control with disturbance observer is proposed. Finally, validity of proposed system is experimented by several simulations.
Top-Down Approaches to Joined-Up Government: Examining the Unintended Consequences of Weak Implementation (2014)

Since forming part of Blair’s modernization agenda in the UK, joined-up government has become a central ambition of governments in many industrialized countries. While there continues to be an absence of core methods and principles for achieving joined-up government, consensus has emerged around the effectiveness of top down approaches. Research has found that joining must happen at multiple levels and be supported by a range of cultural and structural interventions. This article presents findings from a study into the Australian Social Inclusion Agenda and explores the long-term and unintended consequences of joined-up initiatives that take a top-down approach.
Prognostic impact of serum CXC chemokine ligands 4 and 7 on myelodysplastic syndromes post allogeneic hematopoietic cell transplant (2020)

There are a limited number of studies that have evaluated the proteome of myelodysplastic syndrome (MDS) patients [1–9]. Two chemokines (CXCL-4 and CXCL-7) were found to be differentially depressed...
Targeting Robo4-Dependent Slit Signaling to Survive the Cytokine Storm in Sepsis and Influenza (2010)

The innate immune system provides a first line of defense against invading pathogens by releasing multiple inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, which directly combat the infectious agent and recruit additional immune responses. This exuberant cytokine release paradoxically injures the host by triggering leakage from capillaries, tissue edema, organ failure, and shock. Current medical therapies target individual pathogens with antimicrobial agents or directly either blunt or boost the host's immune system. We explored a third approach: activating with the soluble ligand Slit an endothelium-specific, Robo4-dependent signaling pathway that strengthens the vascular barrier, diminishing deleterious aspects of the host's response to the pathogen-induced cytokine storm. This approach reduced vascular permeability in the lung and other organs and increased survival in animal models of bacterial endotoxin exposure, polymicrobial sepsis, and H5N1 influenza. Thus, enhancing the resilience of the host vascular system to the host's innate immune response may provide a therapeutic strategy for treating multiple infectious agents.
Human aldolase A deficiency associated with a hemolytic anemia: thermolabile aldolase due to a single base mutation. (1987)

Fructose-1,6-bisphosphate aldolase A (fructose-bisphosphate aldolase; EC 4.1.2.13) deficiency is an autosomal recessive disorder associated with hereditary hemolytic anemia. To clarify the molecular mechanism of the deficiency at the nucleotide level, we have cloned aldolase A cDNA from a patient's poly(A)+ RNA that was expressed in cultured lymphoblastoid cells. Nucleotide analysis of the patient's aldolase A cDNA showed a substitution of a single nucleotide (adenine to guanine) at position 386 in a coding region. As a result, the 128th amino acid, aspartic acid, was replaced with glycine (GAT to GGT). Furthermore, change of the second letter of the aspartic acid codon extinguished a F ok I restriction site (GGATG to GGGTG). Southern blot analysis of the genomic DNA showed the patient carried a homozygous mutation inherited from his parents. When compared with normal human aldolase A, the patient's enzyme from erythrocytes and from cultured lymphoblastoid cells was found to be highly thermolabile, suggesting that this mutation causes a functional defect of the enzyme. To further examine this possibility, the thermal stability of aldolase A of the patient and of a normal control, expressed in Escherichia coli using expression plasmids, was determined. The results of E. coli expression of the mutated aldolase A enzyme confirmed the thermolabile nature of the abnormal enzyme. The Asp-128 is conserved in aldolase A, B, and C of eukaryotes, including an insect, Drosophila, suggesting that the Asp-128 of the aldolase A protein is likely to be an amino acid residue with a crucial role in maintaining the correct spatial structure or in performing the catalytic function of the enzyme.
ChemInform Abstract: A Short Synthesis of (‐)‐Carbovir (VII). (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Even-parity excited states ofAg−centers in alkali halides (1991)

Two-photon excitation of the ${\mathrm{Ag}}^{\mathrm{\ensuremath{-}}}$ centers in RbCl, RbBr, and KCl have been measured. From the dependence of luminescence on the polarization of the exciting beams, the symmetry of the final levels could be obtained. In all three host crystals, we observed an intense band assigned to the $^{1}$${\mathit{A}}_{1\mathit{g}}$${\ensuremath{\rightarrow}}^{1}$${\mathit{A}}_{1\mathit{g}}$ transition. At higher energies $^{1}$${\mathit{A}}_{1\mathit{g}}$${\ensuremath{\rightarrow}}^{1}$${\mathit{E}}_{\mathit{g}}$ and $^{1}$${\mathit{A}}_{1\mathit{g}}$${\ensuremath{\rightarrow}}^{1}$${\mathit{T}}_{2\mathit{g}}$ transitions could be identified but their presence and intensity change in the different crystals. On the high-energy side of the investigated range, we could observe an intense luminescence signal arising from a two-step excitation process; the exciting photon energy becoming resonant with the $^{3}$${\mathit{T}}_{1\mathit{u}}$ state (A band).
Characterizing Heterogeneous Molecular Biology Database Systems (1995)

Molecular biology data are distributed among multiple databases. Although containing related data, these databases are often isolated and are characterized by various degrees of heterogeneity: they usually represent different views (schemas) of the scientific domain and are implemented using different data management systems. Currently, several systems support managing data in heterogeneous molecular biology databases. Lack of clear criteria for characterizing such systems precludes comprehensive evaluations of these systems or determining their relationships in terms of shared goals and facilities. In this paper, we propose criteria that would facilitate characterizing, evaluating, and comparing heterogeneous molecular biology database systems.
Breast Milk Prefusion F Immunoglobulin G as a Correlate of Protection Against Respiratory Syncytial Virus Acute Respiratory Illness (2018)

Low breast milk pre-F IgG antibodies before RSV ARI support a potential role for pre-F IgG as a correlate of protection against RSV ARI. Induction of breast milk pre-F IgG may be a mechanism of protection for maternal RSV vaccines.
IKK‐β‐mediated myeloid cell activation exacerbates inflammation and inhibits recovery after spinal cord injury (2011)

Traumatic spinal cord injury (SCI) is followed by massive infiltration and activation of myeloid cells such as neutrophils and macrophages, but the functions of these cells are controversial. In this study, our objective was to elucidate the in vivo role of a signaling pathway involved in activation of these innate immune cells in SCI using myeloid cell-specific IκB kinase (IKK)-β conditional knockout (ikkβΔmye) mice. In these mice, the ikkβ gene has been specifically deleted from myeloid cells, compromising their in vivo IKK/NF-κB-dependent activation. We found that ikkβΔmye mice had significantly reduced neutrophil and macrophage infiltrations after SCI compared to ikkβ(+/+) controls. SCI-induced proinflammatory gene expression was also reduced in ikkβΔmye mice. Reduced neuroinflammation in ikkβΔmye mice was accompanied by attenuated neuronal loss and behavioral deficits in motor activity. In addition, the SCI-induced expression of CXC ligand 1 was reduced in ikkβΔmye mice, which may be responsible for the reduced neutrophil infiltration in these mice. Our data demonstrate that IKK-β-dependent myeloid cell activation potentiates neuroinflammation and neuronal damage after SCI.
Molecular Mechanisms of Zinc-Dependent Leukocyte Adhesion Involving the Urokinase Receptor and β2-Integrins (1999)

The trace element Zinc (Zn2+) has been implicated as a mediator in host defense, yet the molecular basis for its extracellular functions remains obscure. Here, we demonstrate that Zn2+can induce the adhesion of myelomonocytic cells to the endothelium, as well as to the provisional matrix proteins vitronectin (VN) and fibrinogen (FBG), which are pivotal steps for the recruitment of leukocytes into inflamed/injured tissue. Physiologic concentrations of Zn2+ increased the urokinase receptor (uPAR)-mediated adhesion of myelomonocytic cells to VN, whereas other divalent cations had smaller effects. Zn2+-induced cell adhesion to VN was abolished by cation chelators such as 1-10-phenanthroline, as well as by plasminogen activator inhibitor-1 (PAI-1) and a monoclonal antibody (MoAb) against uPAR. These characteristics could be recapitulated with a uPAR-transfected cell line emphasizing the specificity of this receptor system for Zn2+-dependent cell adhesion. Like urokinase (uPA), Zn2+ increased the binding of radiolabeled VN to uPAR-expressing cells, as well as the interaction of VN with immobilized uPAR in an isolated system. Moreover, Zn2+ enhanced leukocytic cell adhesion to FBG and endothelial cell monolayers by activating β2-integrins. Instead of the direct β2-integrin activation through the divalent cation binding site, Zn2+-induced integrin activation was mediated via uPAR, a crucial regulator of this system. The present study uncovers for the first time Zn2+-mediated cell adhesion mechanisms that may play a crucial role in modulating leukocyte adhesion to vessel wall components.
Structural basis of target recognition by Atg8/LC3 during selective autophagy (2008)

Autophagy is a non-selective bulk degradation process in which isolation membranes enclose a portion of cytoplasm to form double-membrane vesicles, called autophagosomes, and deliver their inner constituents to the lytic compartments. Recent studies have also shed light on another mode of autophagy that selectively degrades various targets. Yeast Atg8 and its mammalian homologue LC3 are ubiquitin-like modifiers that are localized on isolation membranes and play crucial roles in the formation of autophagosomes. These proteins are also involved in selective incorporation of specific cargo molecules into autophagosomes, in which Atg8 and LC3 interact with Atg19 and p62, receptor proteins for vacuolar enzymes and disease-related protein aggregates, respectively. Using X-ray crystallography and NMR, we herein report the structural basis for Atg8-Atg19 and LC3-p62 interactions. Remarkably, Atg8 and LC3 were shown to interact with Atg19 and p62, respectively, in a quite similar manner: they recognized the side-chains of Trp and Leu in a four-amino acid motif, WXXL, in Atg19 and p62 using hydrophobic pockets conserved among Atg8 homologues. Together with mutational analyses, our results show the fundamental mechanism that allows Atg8 homologues, in association with WXXL-containing proteins, to capture specific cargo molecules, thereby endowing isolation membranes and/or their assembly machineries with target selectivity.
Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database (2022)

Increasing number of Janus kinase (JAK) inhibitors have been approved for chronic haematopoietic neoplasms and inflammatory/autoimmune diseases. We aimed to assess safety of the first three approved JAK inhibitors: ruxolitinib, tofacitinib and baricitinib. In this retrospective observational study, pharmacovigilance data were extracted from the World Health Organization database. Adverse events are classified according to Medical Dictionary for Regulatory Activities hierarchy. Until February 28, 2021, all Individual Case Safety Reports [ICSRs] with the suspected drug ruxolitinib, tofacitinib or baricitinib were included. Disproportionality analysis was performed and the information component (IC) was estimated. Adverse events were considered a significant signal if the lower end of the 95% credibility interval of the IC (IC025) was positive. We identified 126,815 ICSRs involving JAK inhibitors. Ruxolitinib, tofacitinib and baricitinib were associated with infectious adverse events (IC025 1.7, especially with viral [herpes and influenza], fungal, and mycobacterial infectious disorders); musculoskeletal and connective tissue disorders (IC025 1.1); embolism and thrombosis (IC025 0.4); and neoplasms (IC025 0.8, especially malignant skin neoplasms). Tofacitinib was associated with gastrointestinal perforation events (IC025 1.5). We did not find a significant increase in the reporting of major cardiovascular events. We identified significant association between adverse events and ruxolitinib, tofacinitib and baricitinib in international pharmacovigilance database.