gebhart/patrepeval huggingface dataset:
Novel Aspects of Corrole Chemistry (2005)

Corrole is one of the first examples of porphyrin analogs reported in the literature. This class of compounds has received a great attention, because of their promising exploitation in different fields, ranging from medicine to material chemistry. Among them, corrole can be considered the prototypical example of contracted porphyrins, with one of the meso carbon bridges missing. Although this macrocycle was first reported more than thirty years ago, only recently more attention has been devoted to the chemistry of corrole. The recent availability of efficient and facile syntheses of meso-substituted corroles has probably been the shuttle for the impressive flourishing of corrole-related papers appearing in literature in the last few years. The aim of this review is to highlight the latest reports in the synthetic chemistry of corrole, with special attention to the synthetic strategies and peripheral functionalizations of this macrocycle. Keywords: deprotonation, rothemund method, lindsey method, dipyrromethanes, cyclization, dipyrromethane, n-alkylcorroles
Controlled Growth Factor Delivery for Tissue Engineering (2009)

Growth factors play a crucial role in information transfer between cells and their microenvironment in tissue engineering and regeneration. They initiate their action by binding to specific receptors on the surface of target cells and the chemical identity, concentration, duration, and context of these growth factors contain information that dictates cell fate. Hence, the importance of exogenous delivery of these molecules in tissue engineering is unsurprising, considering their importance for tissue regeneration. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and their potential toxicity at high systemic levels, suggest that conventional routes of administration are unlikely to be effective. In this review, we provide an overview of the design criteria for growth factor delivery vehicles with respect to the growth factor itself and the microenvironment for delivery. We discuss various methodologies that could be adopted to achieve this localized delivery, and strategies using polymers as delivery vehicles in particular.
Active compensation in the switched-capacitor biquad (1983)

One of the limiting factors in the performance of high-ω <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</inf> and high-Q <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</inf> active filters is the finite frequency-dependent gain characteristics of operational amplifiers (op-amps). Investigated here is a simple compensation scheme to reduce the sensitivity of the performance of a switched-capacitor biquad to the finite gain-bandwidth product of the op-amps. Theoretical and experimental results show that the scheme is very useful.
Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau (2008)

Memory loss is the signature feature of Alzheimer's disease, and therapies that prevent or delay its onset are urgently needed. Effective preventive strategies likely offer the greatest and most widespread benefits. Histone deacetylase (HDAC) inhibitors increase histone acetylation and enhance memory and synaptic plasticity. We evaluated the efficacy of nicotinamide, a competitive inhibitor of the sirtuins or class III NAD(+)-dependent HDACs in 3xTg-AD mice, and found that it restored cognitive deficits associated with pathology. Nicotinamide selectively reduces a specific phospho-species of tau (Thr231) that is associated with microtubule depolymerization, in a manner similar to inhibition of SirT1. Nicotinamide also dramatically increased acetylated alpha-tubulin, a primary substrate of SirT2, and MAP2c, both of which are linked to increased microtubule stability. Reduced phosphoThr231-tau was related to a reduction of monoubiquitin-conjugated tau, suggesting that this posttranslationally modified form of tau may be rapidly degraded. Overexpression of a Thr231-phospho-mimic tau in vitro increased clearance and decreased accumulation of tau compared with wild-type tau. These preclinical findings suggest that oral nicotinamide may represent a safe treatment for AD and other tauopathies, and that phosphorylation of tau at Thr231 may regulate tau stability.
Novel radiation sensitizers targeting tissue hypoxia. (1999)

Locally advanced or metastatic adenocarcinoma of the stomach still carries a poor prognosis, with 5-year survival rates of < 15%. Palliative chemotherapeutic regimens for this disease are largely 5-FU-based. We have investigated the clinical activity of an oral combination of uracil and tegafur (UFT) with calcium folinate (Orzel), in patients with measurable metastatic disease. Thirty-six patients received a total of 94 courses of daily UFT 300 mg/m2 plus calcium folinate 90 mg for 28 consecutive days followed by a 7-day rest. Planned treatment doses were maintained in 83% of all evaluable courses. Main toxicities included diarrhea (21 patients) and nausea and vomiting (20 patients). Other side effects were asthenia, malaise, stomatitis, and myelosuppression. At present, 26 patients are evaluable for response. Of these, one achieved a complete response and three achieved partial remissions. In addition, six patients reached stable disease, yielding an overall response rate of 27%. We conclude that the combination of UFT and calcium folinate is a feasible outpatient regimen that warrants further clinical evaluation.
A generalized profile syntax for biomolecular sequence motifs and its function in automatic sequence interpretation. (1994)

A general syntax for expressing biomolecular sequence motifs is described, which will be used in future releases of the PROSITE data bank and in a similar collection of nucleic acid sequence motifs currently under development. The central part of the syntax is a regular structure which can be viewed as a generalization of the profiles introduced by Gribskov and coworkers. Accessory features implement specific motif search strategies and provide information helpful for the interpretation of predicted matches. Two contrasting examples, representing E. coli promoters and SH3 domains respectively, are shown to demonstrate the versatility of the syntax, and its compatibility with diverse motif search methods. It is argued, that a comprehensive machine-readable motif collection based on the new syntax, in conjunction with a standard search program, can serve as a general-purpose sequence interpretation and function prediction tool.
Direct Copper Electroless Deposition on a Tungsten Barrier Layer for Ultralarge Scale Integration (2005)

In the present study, copper is deposited directly on tungsten using an electroless solution. Typically, Cu is deposited on a noble metal seed layer by an electroless process. The seed layers are platinum, palladium (Pd), silver, gold, rhodium, or iridium, while Pd is preferred. It has been proposed that copper (Cu) is deposited on tungsten (W) by a different mechanism. This work has implications for the direct plating of Cu/low k barrier layers. The best deposition conditions were found to be a concentration of 0.0305 mol/L, a solution pH of 11.8, and glyoxylic acid concentration of 0.09 mol/L at 60°C. Under the best conditions for 10 min, the grain shape is spherical, and the surface roughness is ∼11 nm. It is demonstrated that fine-grained, uniform copper film can be obtained for ultralarge scale integrated devices. The thickness of the film was 134 nm for 12 min. The deposition rate was 11.2 nm/min. According to increasing the pH, Cu film is of the phase and the grain shape of Cu is changed. Adjusting the pH resulted in oriented Cu and without impurity peaks during electroless deposition. The roughness of the Cu films depends greatly on the concentration of glyoxylic acid unlike pH changes. The resulting deposited copper concentration was 97 atom % as measured by Rotherford backscattering. The film of Cu/W has good adhesive strength, because a Cu/W alloy forms during electroless deposition. © 2005 The Electrochemical Society. All rights reserved.
Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity (2016)

CSF and serum NfL levels were highly correlated, and serum concentrations were increased in RRMS. Serum NfL levels correlated with MRI markers of WM disease severity. Our findings further support longitudinal studies of serum NfL as a potential biomarker of on-going disease progression and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.
αβ T Cell Receptor Transfer to γδ T Cells Generates Functional Effector Cells without Mixed TCR Dimers In Vivo (2009)

The successful application of T cell-based immunotherapeutic applications depends on the availability of large numbers of T cells with the desired Ag specificity and phenotypic characteristics. Engineering of TCR-transferred T lymphocytes is an attractive strategy to obtain sufficient T cells with an Ag specificity of choice. However, the introduction of additional TCR chains into T cells leads to the generation of T cells with unknown specificity, due to the formation of mixed dimers between the endogenous and introduced TCR chains. The formation of such potentially autoaggressive T cells may be prevented by using gammadelta T cells as recipient cells, but the in vivo activity of such TCR-engineered gammadelta T cells has not been established. In the present study, we have investigated the in vivo functionality of TCR-transduced gammadelta T cells, in particular their Ag specific proliferative capacity, Ag specific reactivity, in vivo persistence, and their capacity to mount recall responses. The results demonstrate that alphabeta TCR engineering of gammadelta T cells forms a feasible strategy to generate Ag-specific effector T cells that do not express mixed TCR dimers. In view of increasing concerns on the potential autoimmune consequences of mixed TCR dimer formation, the testing of alphabeta TCR engineered gammadelta T cells in clinical trials seems warranted.
The respiratory burst oxidase of human neutrophils. Further studies of the purified enzyme. (1986)

A superoxide-forming oxidase from activated human neutrophil membranes was solubilized by two slightly different methods, then purified by "dye-affinity" chromatography. Kinetic studies of the purified preparations gave Vmax values of 5-10 mumol of O-2/min/mg of protein, and Km values for NADH and NADPH that were in reasonable agreement with values determined previously using particulate and crude solubilized preparations of the respiratory burst oxidase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed prominent bands at 67, 48, and 32 kDa, together with some minor contaminants, whereas gel electrophoresis under non-denaturing conditions gave a single major band that when eluted and re-electrophoresed in the presence of sodium dodecyl sulfate showed bands at 67, 48, 32 kDa. We believe that all three bands represent oxidase components. The flavin content of the purified enzyme was 20.4 +/- 2.0 S.E. pmol of FAD/microgram of protein, whereas heme averaged 0.1 +/- 0.02 pmol/microgram and ubiquinone could not be detected. Assuming that the enzyme is composed of one 67-kDa subunit, one 48-kDa subunit, and one 32-kDa subunit (i.e. that its molecular mass is approximately 150 kDa), it can be calculated to have a turnover number of 700-1500 min-1, in agreement with a value reported previously for oxidase in a particulate O-2-forming system (Cross, A. R., Parkinson, J. F., and Jones, O. T. G. (1985) Biochem. J. 226, 881-884), and to contain the following quantities of redox carriers (mol/mol): FAD, 3.0; heme, 0.015; ubiquinone, less than 0.06. It remains to be determined whether this preparation represents the complete respiratory burst oxidase or is only the pyridine nucleotide dehydrogenating component of a more complex enzyme.
QUANTITATIVE ASSESSMENT OF CELL ADHESION MOLECULE GENE EXPRESSION IN ENDOMYOCARDIAL BIOPSY SPECIMENS FROM CARDIAC TRANSPLANT RECIPIENTS USING COMPETITIVE POLYMERASE CHAIN REACTION1 (2000)

ICAM-1 and VCAM-1 gene expression was increased during rejection in endomyocardial biopsy specimens. Competitive polymerase chain reaction can be used to quantitatively assess gene expression in biopsy specimens from patients.
A photo‐CIDNP study of the active sites of Megasphaera elsdenii and Clostridium MP flavodoxins (1982)

Megasphaera elsdenii and Clostridium MP flavodoxins have been investigated by photo-CIDNP techniques. Using time-resolved spectroscopy and external dyes carrying different charges it was possible to assign unambiguously the resonance lines in the NMR-spectra to tyrosine, tryptophan and methionine residues in the two proteins. The results show that Trp-91 in M.elsdenii and Trp-90 in Cl.MP flavodoxin are strongly immobilized and placed directly above the benzene subnucleus of the prosthetic group. The data further indicate that the active sites of the two flavodoxins are extremely similar.
A One-Compartment, Direct Glucose Fuel Cell for Powering Long-Term Medical Implants (2006)

We present the operational concept, microfabrication, and electrical performance of an enzyme-less direct glucose fuel cell for harvesting the chemical energy of glucose from body fluids. The spatial concentrations of glucose and oxygen at the electrodes of the one-compartment setup are established by self-organization, governed by the balance of electro-chemical depletion and membrane diffusion. Compared to less stable enzymatic and immunogenic microbial fuel cells, this robust approach excels with an extended life time, the amenability to sterilization and biocompatibility, showing up a clear route towards an autonomous power supply for long-term medical implants without the need of surgical replacement and external refueling. Operating in physiological phosphate buffer solution containing 0.1 wt% glucose and having a geometrical cathode area of 10 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , our prototype already delivers 20 µ W peak power over a period of 7 days.
Primary structure and functional expression of a choline transporter expressed in the rat nervous system (1992)

Synthesis of the neurotransmitter acetylcholine in cholinergic nerve terminals is regulated by a sodium‐driven high‐affinity choline uptake system in the plasma membrane. We have isolated cDNAs from rat spinal cord and brainstem which encode a choline transporter (CHOT1). The predicted protein shares considerable amino acid identity and several structural features including twelve putative transmembrane regions with other neurotransmitter transporters. Expression of in vitro transcribed CHOT1 RNA in Xenopus oocytes generated Na + ‐dependent choline uptake, which was not seen in control oocytes. Amplification by polymerase chain reaction (PCR) revealed significant amounts of CHOT1 mRNA in brain, cerebellum, spinal cord and, to a lesser extent, heart, but only very low expression in lung, kidney and muscle.
A Role for the Basal Forebrain Cholinergic System in Estrogen-Induced Disinhibition of Hippocampal Pyramidal Cells (2003)

Estrogen transiently disinhibits hippocampal CA1 pyramidal cells in adult female rats and prolongs the decay time of IPSCs in these cells. Estrogen-induced changes in synaptic inhibition are likely to be causally related to subsequent enhancements in excitatory synaptic function in CA1 pyramidal cells. Currently, it is unknown how or on what cells estrogen acts to regulate synaptic inhibition in the hippocampus. We used whole-cell voltage-clamp recording of synaptically evoked IPSCs, spontaneous IPSCs, and miniature IPSCs in CA1 pyramidal cells to evaluate estrogen-induced changes in synaptic inhibition in ovariectomized rats that either were pretreated with the estrogen receptor (ER) antagonist tamoxifen or in which basal forebrain cholinergic neurons were eliminated by previous infusion of 192IgG-saporin toxin into the medial septum. We found that estrogen-induced disinhibition and prolongation of IPSCs are entirely dependent on a tamoxifen-sensitive ER. Estrogen-induced disinhibition is partially dependent on basal forebrain cholinergic neurons, but the prolongation of IPSCs is not at all dependent on these cells. Paired-pulse experiments and recordings of action potential-related spontaneous IPSCs suggest that estrogen-induced disinhibition is associated with a decrease in probability of release at GABAergic synapses, which decreases the amplitude of IPSCs produced by inhibitory neuron action potentials. Our findings lend novel insights into estrogen regulation of inhibitory synapses in the hippocampus and point to estrogen action on basal forebrain cholinergic neurons as critically involved in mediating the effects of estrogen in the hippocampus.
Aorta Remodeling Responses to Distinct Atherogenic Stimuli: Hyperten-sion, Hypercholesterolemia and Turbulent Flow/Low Wall Shear Stress (2008)

This review is based on recently published data from our laboratory. We investigated the role of hypertension and laminar flow, hypercholesterolemia and laminar flow and turbulent blood flow/low wall shear stress, and turbulent blood flow/low wall shear stress associated with hypercholesterolemia on aorta remodeling of rats feeding normal diet or hypercholesterolemic diet. Our findings suggest that increased circumferential wall tension due to hypertension plays a key role in the remodeling through biomechanical effects on oxidative stress and increased TGF-beta expression; the remodeling observed in the presence of hypercholesterolemia could be initiated by oxidative stress that is involved in several processes of atherogenesis and this remodeling is more pronounced in the presence of turbulent blood flow/low wall shear stress.
Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers (2000)

The effects of thrombopoietic stimulation on megakaryocytopoiesis, platelet production, and platelet viability and function were examined in normal volunteers randomized to receive single bolus subcutaneous injections of 3 microg/kg pegylated recombinant megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo in a 3:1 ratio. PEG-rHuMGDF transiently doubled circulating platelet counts, from 237 +/- 41 x 10(3)/microL to 522 +/- 90 x 10(3)/microL (P <.0001), peaking on day 12. Baseline and day-12 samples showed no differences in responsiveness of platelets to adenosine diphosphate or thrombin receptor agonist peptide (P >.4 in all cases); expression of platelet ligand-induced binding sites or annexin V binding sites (P >.6 in both cases); or density of platelet TPO-receptors (P >.5). Platelet counts normalized by day 28. The life span of autologous (111)In-labeled platelets increased from 205 +/- 18 hours (baseline) to 226 +/- 22 hours (P <.01) on day 8. Platelet life span decreased from 226 +/- 22 hours (day 8) to 178 +/- 53 hours (P <.05) on day 18. The theoretical basis for senescent changes in mean platelet life span was illustrated by biomathematical modeling. Platelet turnover increased from 43.9 +/- 11.9 x 10(3) platelets/microL/d (baseline) to 101 +/- 27.6 x 10(3) platelets/microL/d (P =.0009), and marrow megakaryocyte mass expanded from 37.4 +/- 18.5 fL/kg to 62 +/- 17 x 10(10) fL/kg (P =. 015). Although PEG-rHuMGDF initially increased megakaryocyte volume and ploidy, subsequently ploidy showed a transient reciprocal decrease when the platelet counts exceeded placebo values. In healthy human volunteers PEG-rHuMGDF transiently increases megakaryocytopoiesis 2-fold. Additionally, peripheral platelets expand correspondingly and exhibit normal function and viability during the ensuing 10 days. The induced perturbation in steady state thrombopoiesis resolves by 4 weeks. (Blood. 2000;95:2514-2522)
Long-term in vivo survival of receptor-modified syngeneic T cells in patients with human immunodeficiency virus infection. (2000)

To study human immunodeficiency virus (HIV)-specific cellular immunity in vivo, we transferred syngeneic lymphocytes after ex vivo expansion and transduction with a chimeric receptor gene (CD4/CD3-zeta) between identical twins discordant for HIV infection. Single and multiple infusions of 10(10) genetically modified CD8(+) T cells resulted in peak fractions in the circulation of approximately 10(4) to 10(5) modified cells/10(6) mononuclear cells at 24 to 48 hours, followed by 2- to 3-log declines by 8 weeks. In an effort to provide longer high-level persistence of the transferred cells and possibly enhance anti-HIV activity, we administered a second series of infusions in which both CD4(+ )and CD8(+) T cells were engineered to express the chimeric receptor and were costimulated ex vivo with beads coated with anti-CD3 and anti-CD28. Sustained fractions of approximately 10(3) to 10(4) modified cells/10(6) total CD4(+) or CD8(+) cells persisted for at least 1 year. Assessment of in vivo trafficking of the transferred cells by lymphoid tissue biopsies revealed the presence of modified cells in proportions equivalent to or below those in the circulation. The cell infusions were well tolerated and were not associated with substantive immunologic or virologic changes. Thus, adoptive transfer of genetically modified HIV-antigen-specific T cells was safe. Sustained survival in the circulation was achieved when modified CD4(+ )and CD8(+) T cells were infused together after ex vivo costimulation, indicating the important role played by antigen-specific CD4(+) T cells in providing "help" to cytotoxic effectors. (Blood. 2000;96:467-474)
Immunoprotective potential of polysaccharide-tetanus toxoid conjugate in Klebsiella pneumoniae induced lobar pneumonia in rats. (2005)

The polysaccharide (PS) derived from K. pneumoniae NCTC 5055 lipopolysaccharide (LPS) was covalently linked to tetanus toxoid by using carbodimide with adipic acid dihydrazide as a spacer molecule. The conjugate was found to be non-toxic and non-pyrogenic at 100 microg dose level. At a similar dose, the conjugate did not elicit any local skin reaction on intradermal preparatory injection in rabbits. The conjugate was immunoprotective as was evident from the decrease in relative colonization of bacteria in lungs of immunized rats as compared to the control animals. Immunization with the conjugate resulted in alveolar macrophage activation in terms of their ability to phagocytose bacteria in vitro.
Multiple Metal–Carbon Bonds for Catalytic Metathesis Reactions (Nobel Lecture) (2006)

Metathesis reactions are among the most important processes in organic synthesis. The decisive breakthrough in making these reactions practical for industrial purposes, which range from the synthesis of polymers to pharmaceuticals, came with the discovery of the reaction mechanism by Yves Chauvin and the targeted development of transition-metal-based metathesis catalysts by Richard Schrock and Robert Grubbs. The winners of the Chemistry Nobel Prize in 2005 present first-hand accounts of these developments.
LORAKS makes better SENSE: Phase‐constrained partial fourier SENSE reconstruction without phase calibration (2016)

The SENSE-LORAKS framework provides promising new opportunities for highly accelerated MRI. Magn Reson Med 77:1021-1035, 2017. © 2016 International Society for Magnetic Resonance in Medicine.