gebhart/patrepeval huggingface dataset:
Inhibition of neutrophil-mediated production of reactive oxygen species (ROS) by endothelial cells is not impaired in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis patients (2010)

Leucocyte transendothelial migration is strictly regulated to prevent undesired inflammation and collateral damage of endothelial cells by activated neutrophils/monocytes. We hypothesized that in anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV) patients' dysregulation of this process might underlie vascular inflammation. Peripheral blood mononuclear cells (PBMC) and neutrophils from AAV patients (n = 12) and healthy controls (HC, n = 12) were isolated. The influence of human umbilical vein endothelial cells (HUVEC) on neutrophil/monocytes function was tested by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP)- and phorbol 12-myristate 13-acetate (PMA)-mediated ROS production, degranulation and interleukin (IL)-8 production. In addition, the ability of lipopolysaccharide (LPS)-stimulated PBMC to produce tumour necrosis factor (TNF)-alpha in the presence or absence of HUVEC was tested. HUVEC inhibited ROS production dose-dependently by fMLP-stimulated neutrophils but did not influence degranulation. No differences between neutrophils from HC and AAV were found. However, in only one active patient was degranulation inhibited significantly by HUVEC only before cyclophosphamide treatment, but not 6 weeks later. Co-cultures of HUVEC with LPS-stimulated neutrophils/monocytes increased IL-8 production while TNF-alpha production was inhibited significantly. There was no apparent difference between AAV patients and HC in this respect. Our findings demonstrate that HUVEC are able to inhibit ROS and modulate cytokine production upon stimulation of neutrophils or monocytes. Our data do not support the hypothesis that endothelial cells inhibit ROS production of neutrophils from AAV patients inadequately. Impaired neutrophil degranulation may exist in active patients, but this finding needs to be confirmed.
Tumor Suppressor 101F6 and Ascorbate Synergistically and Selectively Inhibit Non–Small Cell Lung Cancer Growth by Caspase-Independent Apoptosis and Autophagy (2007)

101F6 is a candidate tumor suppressor gene harbored on chromosome 3p21.3, a region with frequent and early allele loss and genetic alterations in many human cancers. We previously showed that enforced expression of wild-type 101F6 by adenoviral vector-mediated gene transfer significantly inhibited tumor cell growth in 3p21.3-deficient non-small cell lung cancer (NSCLC) cells in vitro and in vivo. The molecular mechanism of 101F6-mediated tumor suppression is largely unknown. A computer-aided structural and functional model predicts the 101F6 protein to be a member of the cytochrome b561 protein family that is involved in the regeneration of the antioxidant ascorbate. 101F6 protein is expressed in normal lung bronchial epithelial cells and fibroblasts but is lost in most lung cancers. Treatment with 101F6 nanoparticle-mediated gene transfer in combination with a subpharmacologic dose (200-500 micromol/L) of ascorbate synergistically and selectively inhibited lung cancer cell growth in vitro. Systemic injection of 101F6 nanoparticles plus the i.p. injection of ascorbate synergistically inhibited both tumor formation and growth in human NSCLC H322 orthotopic lung cancer mouse models (P<0.001). Furthermore, exogenous expression of 101F6 enhanced intracellular uptake of ascorbate, leading to an accumulation of cytotoxic H(2)O(2) and a synergistic killing of tumor cells through caspase-independent apoptotic and autophagic pathways. The antitumor synergism showed by the combination treatment with systemic administration of 101F6 nanoparticles and ascorbate on lung cancer offers an attractive therapeutic strategy for future clinical trials in cancer prevention and treatment.
Enzyme-activatable imaging probe reveals enhanced neutrophil elastase activity in tumors following photodynamic therapy (2013)

We demonstrate the use of an enzyme-activatable fluorogenic probe, Neutrophil Elastase 680 FAST (NE680), for in vivo imaging of neutrophil elastase (NE) activity in tumors subjected to photodynamic therapy (PDT). NE protease activity was assayed in SCC VII and EMT6 tumors established in C3H and BALB/c mice, respectively. Four nanomoles of NE680 was injected intravenously immediately following PDT irradiation. 5 h following administration of NE680, whole-mouse fluorescence imaging was performed. At this time point, levels of NE680 fluorescence were at least threefold greater in irradiated versus unirradiated SCC VII and EMT6 tumors sensitized with Photofrin. To compare possible photosensitizer-specific differences in therapy-induced elastase activity, EMT6 tumors were also subjected to 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH)-PDT. NE levels measured in HPPH-PDT-treated tumors were twofold higher than in unirradiated controls. Ex vivo labeling of host cells using fluorophore-conjugated antibodies and confocal imaging were used to visualize Gr1+ cells in Photofrin-PDT-treated EMT6 tumors. These data were compared with recently reported analysis of Gr1+ cell accumulation in EMT6 tumors subjected to HPPH-PDT. The population density of infiltrating Gr1+ cells in treated versus unirradiated drug-only control tumors suggests that the differential in NE680 fold enhancement observed in Photofrin versus HPPH treatment may be attributed to the significantly increased inflammatory response induced by Photofrin-PDT. The in vivo imaging of NE680, which is a fluorescent reporter of NE extracellular release caused by neutrophil activation, demonstrates that PDT results in increased NE levels in treated tumors, and the accumulation of the cleaved probe tracks qualitatively with the intratumor Gr1+ cell population.
A Non-Covalent Peptide-Based Strategy for siRNA Delivery (2010)

The development of short-interfering RNA (siRNA) has provided great hope for therapeutic targeting of specific genes responsible for pathological disorders. However, the poor cellular uptake of siRNA together with the low permeability of the cell membrane to negatively charged molecules, remain major obstacles to clinical development. So far there is no universal method for siRNA delivery as they all present several limitations. Several non-viral strategies have been proposed to improve the delivery of synthetic siRNAs in both cultured cells and in vivo. Cell-penetrating peptides (CPPs) or protein transduction domains (PTD) constitute very promising tools for non-invasive cellular import of siRNA and non-covalent CPP/PTD-based strategies have been successfully applied for ex vivo and in vivo delivery of therapeutic siRNA molecules. We recently described a new peptide-based system, CADY, for efficient delivery of siRNA in both primary and suspension cell lines. CADY is a secondary amphiphatic peptide able to form stable non-covalent complexes with siRNA and to improve their cellular uptake independently of the endosomal pathway. This chapter describes easy to handle protocols for the use of the CADY-nanoparticle technology for the delivery of siRNA into both adherent and suspension cell lines. It will also highlight different critical points in the peptide/siRNA complex preparation and transfection protocols, in order to obtain siRNA-associated interfering response at low nanomolar concentration.
Password-Protected Secret Sharing. (2010)

We revisit the problem of protecting user’s private data against adversarial compromise of user’s device(s) which would normally store this data. We formalize an attractive solution to this problem as PasswordProtected Secret-Sharing (PPSS), which is a protocol that allows a user to secret-share her data among n trustees in such a way that (1) the user can retrieve the shared secret upon entering a correct password into a reconstruction protocol which succeeds as long as at least t+ 1 honest trustees participate, and (2) the shared data remains secret even against the adversary which corrupts at most t servers, with the level of protection expected of passwordauthentication, i.e. the probability that the adversary learns anything useful about the secret is at most negligibly greater than q/|D| where q is the number of reconstruction protocol instances in which adversary engages and |D| is the size of the dictionary from which the password was randomly chosen. We propose an efficient PPSS protocol in the public key model, i.e. where the device can remember a trusted public key, provably secure under the DDH assumption, using non-interactive zero-knowledge proofs which are efficiently instantiatable in the Random Oracle Model (ROM). The resulting protocol is robust and practical, with fewer than 4t + 12 exponentiations per party, and with only three messages exchanged between the user and each server, implying a single round of interaction in the on-line phase. As a side benefit our PPSS protocol yields a new Threshold Password Authenticated Key Exchange (T-PAKE) protocol in the public key model which is significantly faster than existing T-PAKE’s provably secure in the public key model in ROM.
Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials (2023)

Cancer Research UK, UK Medical Research Council.
Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior (2007)

Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of serotonergic neurons, different from the subset of serotonergic neurons activated by anxiogenic stimuli or uncontrollable stressors. Consequently, selective activation of specific subsets of serotonergic neurons may have distinct behavioral outcomes.
Investigation of the Coordination Interactions of S-(Pyridin-2-ylmethyl)-l-Cysteine Ligands with M(CO)3+ (M = Re, 99mTc) (2009)

Development of new ligands for fac-M(OH(2))(3)(CO)(3)(+) (M = Re, (99m)Tc) led the investigation with S-(pyridin-2-ylmethyl)-l-cysteine, 1. The ligand 1 has potential to coordinate with the metal through three different tridentate modes: tripodal through cysteine (O,N,S) and two linear involving the S-pyridyl and cysteine (O,S,N(Py), N,S,N(Py)). From the reaction with 1, two species were observed in the (1)H NMR, where the primary product was the linear fac-Re(N,S,N(Py)-1)(CO)(3)(+), 2a, complex. To identify the coordination mode of the minor product, functionalized analogues of 1 were prepared from S-(pyridin-2-ylmethyl)-Boc-l-cysteine-methyl ester, 3, with orthogonal protecting groups on the C terminus (methyl ester) in S-(pyridin-2-ylmethyl)-l-cysteine methyl ester, 4, or N terminus (Boc) in S-(pyridin-2-ylmethyl)-Boc-l-cysteine, 6, that specifically directed the coordination mode of fac-M(H(2)O)(3)(CO)(3)(+) to either N,S,N(Py) or O,S,N(Py), respectively. Two diastereomers [fac-Re(CO)(3)(N,S,N(Py)-4)](+), 5a and 5b, were observed and independently characterized by X-ray structure analysis and NMR in high yield with 4. Surprisingly, the O,S,N(Py) Re complex with ligand 6 was not observed and simplified versions, 3-(pyridin-2-ylmethylthio) propanoic acid, 7, and 2-(pyridin-2-ylmethylthio)acetic acid, 8, were investigated. Ligand 7 did not yield the desired linear tridentate O,S,N(Py) product. However, the shorter ligand 8 formed fac-Re(CO)(3)(O,S,N(Py)-8), 9, in high yield. (99m)Tc labeling studies were conducted and yielded similar results to the rhenium complex and effective (>99%) at 10(-5) M ligand concentration.
Derivatization of Dinitrogen by Molybdenum in Triamidoamine Complexes (1998)

The reduction of [N3N]MoCl by an excess of Mg powder in THF under dinitrogen (1 atm) yields the diazenido species {[N3N]Mo−NN}2Mg(THF)2 (1), which reacts with MCl2(PPh3)2 (M = Ni or Pd) or ZnCl2 to yield [N3N]Mo(N2) (2). Heating toluene solutions of 2 under dinitrogen yields the homobimetallic dinitrogen complex [N3N]Mo−NN−Mo[N3N] (3). Derivatization of dinitrogen is achieved by reaction of 1 with (TMS)Cl to yield the diazenido complex [N3N]Mo−NN−TMS (4). 4 reacts with an excess of MeOTf to give two products, the dimethyl hydrazido complex {[N(CH2CH2NSiMe3)2(CH2CH2NCH3)]MoN−NMe2}OTf (5) and the diazenido complex {[(Me3SiNCH2CH2)2NCH2CH2NMe2]Mo−NNSiMe3}OTf (6). Both 5 and 6 react readily with MeMgCl to yield products arising from methylation at molybdenum, [N(CH2CH2NSiMe3)2(CH2CH2NMe2)]Mo(CH3)(N2TMS) (7) and [N(CH2CH2NSiMe3)2(CH2CH2NMe)]Mo(CH3)(NNMe2) (8), respectively. In 7, the dimethylamino group is not bound to the metal. Compound 8 is thermally unstable, decomposing via N−N bond cleavage to yield the nitrido complex [(Me3SiNCH2CH2)2N(CH2CH2NMe)]Mo⋮N (9). X-ray studies are reported for compounds 1, 2, 5, 6, and 7.
Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs (2013)

CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are Vα14Jα18(+) invariant NKT (iNKT) cells that recognize the prototypical α-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) α-and β-chains, does not recognize α-galactosylceramide, and is referred to as diverse NKT (dNKT) cells. dNKT cells play important roles during infection and autoimmunity, but the antigens they recognize remain poorly understood. Here, we identified phosphatidylglycerol (PG), diphosphatidylglycerol (DPG, or cardiolipin), and phosphatidylinositol from Mycobacterium tuberculosis or Corynebacterium glutamicum as microbial antigens that stimulated various dNKT, but not iNKT, hybridomas. dNKT hybridomas showed distinct reactivities for diverse antigens. Stimulation of dNKT hybridomas by microbial PG was independent of Toll-like receptor-mediated signaling by antigen-presenting cells and required lipid uptake and/or processing. Furthermore, microbial PG bound to CD1d molecules and plate-bound PG/CD1d complexes stimulated dNKT hybridomas, indicating direct recognition by the dNKT cell TCR. Interestingly, despite structural differences in acyl chain composition between microbial and mammalian PG and DPG, lipids from both sources stimulated dNKT hybridomas, suggesting that presentation of microbial lipids and enhanced availability of stimulatory self-lipids may both contribute to dNKT cell activation during infection.
Molecular Genetics of the Human Cytochrome P450-Dependent Monooxygenases. (1992)

In this work, the role of genetic as well as environmental factors in determining cytochrome P450 isozyme levels in man have been studied. Simple DNA based assays for the identification of individuals nulled at the CYP2D6 locus are described and have been applied to investigate whether this gene defect is associated with altered cancer susceptibility. In contrast to literature reports, in no cancer type were poor metabolizers underrepresented, indeed in several cancers the mutant allele frequency was increased. A model using human tumours grown as xenografts is described that should help elucidate the factors which regulate P450 levels in man.
A Designed β-Hairpin Containing a Natural Hydrophobic Cluster (2000)

„Designer-Haarnadeln”︁: Das aus zwölf Aminosäuren, darunter D-Prolin, bestehende Peptid 1 faltet sich in wässriger Lösung unter Bildung eines zweisträngigen antiparallelen β-Faltblatts, wodurch sich die Seitenketten von Trp 2, Tyr 4, Phe 11 und Val 13 sehr nahe kommen (im Bild hervorgehoben). Ähnliches wird beim Protein GB1 im gefalteten Zustand beobachtet. Thermodynamische Untersuchungen sprechen dafür, dass ein hydrophober Effekt und Wechselwirkungen innerhalb des Peptids zur Stabilität der β-Haarnadelschleife beitragen.
Peripheral capillary non-perfusion in treatment-naïve proliferative diabetic retinopathy associates with postoperative disease activity 6 months after panretinal photocoagulation (2018)

We found the area of PCNP at all timepoints to be statistically larger in patients with active PDR 6 months after PRP treatment. Therefore, the area of PCNP, at baseline, may serve as a potential predictive marker for PDR activity after treatment.
A Magnetic Separation Method to Improve Signal‐to‐Noise Ratio in the Measurement of Iron Deficiency Biomarkers Using a Photonic Crystal Biosensor Immunoassay (2015)

Point‐of‐care diagnostics are critically needed to identify populations that are at risk or suffering from iron deficiency anemia (IDA). Current biosensing immunoassays capable of measuring IDA biomarkers, e.g. soluble transferrin receptor (sTfR), require extensive sample preparation to reduce non‐specific binding. In this study, the authors harnessed the magnetic properties of iron‐oxide nanoparticles (IONS) conjugated with antibodies (Ab) to reduce non‐specific binding and to increase signal‐to‐noise ratio. The objectives were to 1) establish a magnetic separation protocol to evaluate binding of sTfR (85 kDa) in a dose‐response fashion using anti‐sTfR functionalized with 30‐nm IONs (Fab‐IONs), and 2) compare the accuracy of this method in quantifying WHO's sTfR reference standard with an FDA‐certified ELISA. Fab‐IONs (0.25 mg/ml) were used as immuno‐probes to separate sTfR (0.005‐0.5 µg/ml) from different media. Binding occurred while shaking samples for 2 h at 450 rpm. A neodymium magnet separated the Fab‐IONs and sTfR complexes. Supernatants and complexes were loaded onto a 384‐well photonic crystal (PC) biosensor microplate functionalized with capture Ab. The PC biosensor showed linear (R 2 =0.99) response [PWV=8.3 (µg/ml) ‐ 0.1253]. The analytical bias when measuring the WHO reference standard either with the ELISA (‐3.40 µg/ml, 95% CI [‐6.59 ― 0.21]) or the PC biosensor (‐2.54 µg/ml; 95% CI [‐5.16 ― 0.7]) was similar (p&gt;0.05). Magnetic separation using Fab‐IONs is a promising method to measure key nutrition biomarkers at the point of care.
Gallium Concentration Optimisation of Gallium Doped Zinc Oxide for Improvement of Optical Properties (2021)

Abstract The near-band luminescence of doped ZnO is promising for advanced scintillators; however, the dopant type and concentration effects require a detailed study. Undoped and Ga-doped ZnO nanopowders were prepared by a microwave-assisted solvothermal method and the gallium concentration effect on luminescence properties was studied. The near-band luminescence peak position dependence on gallium concentration was observed. Near-band luminescence intensity versus defect luminescence intensity ratio was explored for different gallium concentrations and the optimal value was determined. Samples were prepared with dopant concentrations between 0.2 and 1.5 at%, XRD analysis confirmed that samples contained only zinc oxide hexagonal wurtzite phase. The results of the research showed that ZnO:Ga containing 0.9 at.% gallium was promising for scintillators.
Considerations for the development of cost‐effective cell culture media for cultivated meat production (2020)

Innovation in cultivated meat development has been rapidly accelerating in recent years because it holds the potential to help attenuate issues facing production of dietary protein for a growing world population. There are technical obstacles still hindering large-scale commercialization of cultivated meat, of which many are related to the media that are used to culture the muscle, fat, and connective tissue cells. While animal cell culture media has been used and refined for roughly a century, it has not been specifically designed with the requirements of cultivated meat in mind. Perhaps the most common industrial use of animal cell culture is currently the production of therapeutic monoclonal antibodies, which sell for orders of magnitude more than meat. Successful production of cultivated meat requires media that is food grade with minimal cost, can regulate large-scale cell proliferation and differentiation, has acceptable sensory qualities, and is animal ingredient-free. Much insight into strategies for achieving media formulations with these qualities can be obtained from knowledge of conventional culture media applications and from the metabolic pathways involved in myogenesis and protein synthesis. In addition, application of principles used to optimize media for large-scale microbial fermentation processes producing lower value commodity chemicals and food ingredients can also be instructive. As such, the present review shall provide an overview of the current understanding of cell culture media as it relates to cultivated meat.
ChemInform Abstract: AN ASYMMETRIC SYNTHESIS OF THE DIASTEREOMERIC 1‐(2‐CYCLOHEXENYL)‐1‐ALKANOLS IN HIGH OPTICAL PURITY VIA A STEREOCHEMICALLY STABLE ALLYLIC BORANE, B‐2‐CYCLOHEXEN‐1‐YLDIISOPINOCAMPHEYLBORANE (1985)

Abstract Hydroborierung von 1,3‐Cyclohexadien (I) mit dem Bor‐Reagens (II) ergibt mit hoher Selektivität das chirale Boran (III).