Miracle-dz/UniFAR-FTUs huggingface dataset:
Symmetrical and Non-symmetrical meso-meso Directly-Linked Hydroporphyrin Dyads: Synthesis and Photochemical Properties

A series of a rigid meso-meso directly-linked chlorin-chlorin, chlorin-bacteriochlorin, and bacteriochlorin-bacteriochlorin dyads, including free bases as well as Zn(II), Pd(II) and Cu(II) complexes has been synthesized, and their absorption, emission, singlet oxygen ( 1 O 2 ) photosensitization, and electronic properties have been examined. Marked bathochromic shift of the long-wavelength Q y absorption band and increase in fluorescence quantum yields in dyads, compared to the corresponding monomers, are observed. Non-symmetrical dyads (except bacteriochlorin-bacteriochlorin) show two distinctive Q y bands, corresponding to the absorption of each dyad component. A nearly quantitative S 1 -S 1 energy transfer between hydroporphyrins in dyads, leading to an almost exclusive emission of hydroporphyrin with a lower S 1 energy, have been determined. Several symmetrical and all non-symmetrical dyads exhibit a significant reduction of fluorescence quantum yields in solvents of high dielectric constants; this is attributed to the photoinduced electron transfer. The complexation of one macrocycle by Cu(II) or Pd(II) enhances intersystem crossing in the adjacent, free base dyad component, which is manifested by a significant reduction in fluorescence and increase in quantum yield of 1 O 2 photosensitization. Graphical abstract Symmetrical and non-symmetrical meso-meso linked chlorin-chlorin, chlorin bacteriochlorin and bacteriochlorin-bacteriochlorin dyads, (free base and Zn(II), Pd(II) or Cu(II) complexes) are reported. For non-symmetrical dyads an efficient singlet-singlet energy transfer is observed. Insertion of heavy element [Pd(II) or Cu(II)] significantly enhances 1 O 2 photosensitization. Most of the dyads exhibit a significant reduction of the fluorescence in highly polar solvents, suggesting a charge transfer character of the excited state.
Signatures of Protective Memory Immune Responses During HCV Reinfection

Background & Aims— Development of a vaccine against hepatitis C virus (HCV) has been hindered by our limited understanding of immune correlates of protection during real-life exposure to the virus. We studied the immune response during HCV reinfection. Methods— We analyzed blood samples from participants in the Montreal Acute Hepatitis C Injection Drug User Cohort Study who were re-infected with HCV from 2009 and 2012. Five patients spontaneously resolved their second infection while 4 developed chronic infections. We monitored the phenotypic and functional dynamics of HCV-specific memory responses of T cells from all subjects, during natural re-exposure and reinfection. Results— Populations of CD4+ and CD8+ T cells with HCV-specific polyfunctional memory were expanded in all 5 individuals who resolved 2 successive HCV infections. We detected the CD127 hi HCV-specific memory CD8+ T cells prior to reinfection regardless of a subject’s ability to clear subsequent infections. Protection against viral persistence was associated with the expansion of a CD127 neg , PD1 lo effector memory T cells at the peak of the response. We also observed broadening of T-cell response, indicating generation of de novo T-cell responses. The 4 individuals who failed to clear their subsequent infection had limited expansion of HCV-specific CD4+ and CD8+ memory T cells and expressed variable levels of the exhaustion marker PD1 on HCV-specific CD8+ T cells. Dominant epitope regions of HCV strains isolated from patients with persistent reinfection had sequence variations that were not recognized by the pre-existing memory T cells. Conclusions— Protection from persistent HCV reinfection depends on the magnitude, breadth, and quality of the HCV-specific memory T-cell response. Sequence homology among viruses, and ability of T cells to recognize multiple strains of HCV, are critical determinants of protective memory.
Early detection of hand movements from EEGs for stroke therapy applications

Movement-assist devices such as neuromuscular stimulation systems can be used to generate movements in people with chronic hand paralysis due to stroke. If detectable, motor planning activity in the cortex could be used in real time to trigger a movement-assist device and restore a person’s ability to perform many activities of daily living. Additionally, re-coupling motor planning in the cortex with assisted movement generation in the periphery may provide an even greater benefit—strengthening relevant synaptic connections over time to promote natural motor recovery. This study examined the potential for using electroencephalograms (EEGs) as a means of rapidly detecting the intent to open the hand during movement planning in individuals with moderate chronic hand paralysis following a subcortical ischemic stroke. Attempts to open the hand on average could be detected from EEGs approximately 100–500 ms prior to the first signs of movement onset. This earlier detection would minimize device activation delays and would allow for tighter coupling between initial formation of the motor plan in the cortex and augmentation of that plan in the periphery by a movement-assist device. This tight temporal coupling may be important or even essential for strengthening synaptic connections and enhancing natural motor recovery.
Fibroblasts lead the way: a unified view of three-dimensional cell motility

Primary human fibroblasts are remarkably adaptable, able to migrate in differing types of physiological 3D tissue and on rigid 2D tissue culture surfaces. The crawling behavior of these and other vertebrate cells has been studied intensively, which has helped generate the concept of the cell motility cycle as a comprehensive model of 2D cell migration. However, this model fails to explain how cells force their large nuclei through the confines of a 3D matrix environment and why primary fibroblasts can use more than one mechanism to move in 3D. Recent work shows that the intracellular localization of myosin II activity is governed by cell-matrix interactions to both force the nucleus through the extracellular matrix and dictate the type of protrusions used to migrate in 3D. lamellipodia-independent protrusion. While Rac1, Cdc42, and PIP3 signaling are nonpolarized in these polarized cells, microtubules might provide polarity in response to matrix topography. (B) 2D and 3D lamellipodia-based movement. Membrane protrusion by actin polymerization allows the formation of new membrane-matrix contacts. Actomyosin contractility throughout the cell strengthens these adhesions and increases cellular tension without increasing intracellular pressure. Adhesions disassemble at the back of the cell, and actomyosin contractility retracts the trailing edge to help the cell body glide forward. Polarized signaling by Rac1, Cdc42, and PIP3 coordinates protrusion and adhesion formation. Microtubules deliver additional polarity cues to the front of the cell, along with membrane and lipid components. (C) Adhesion-independent “amoeboid” fibroblast 3D motility. When cells are not strongly adherent to the substrate, myosin II-driven retrograde flow of actomyosin occurs only in the very leading protrusions and likely leads to a relative uniform distribution of myosin II in the cell cortex. These cells are unable to generate productive forward movement on a 2D surface. However, when these cells are compressed between two surfaces, the resulting friction is sufficient to translate force, presumably from the retrograde flow of the cortical cytoskeleton, into forward movement of the cell. See Box 1 for a discussion of how the physical structure of the matrix can help determine 3D migration mechanisms.
Origin and Development In Vitro of Shoot Buds and Somatic Embryos from Intact Roots of Helianthus annuus 3 H. tuberosus

A variant clone of the tetraploid (2 n = 4 x = 68) interspeciﬁc hybrid Helianthus annuus 3 H. tuberosus derived by in vitro tissue culture showed a deviation from the usual pattern of organization of the plant body. This variant developed shoot-like structures and somatic embryos from intact adventitious roots of in vitro -grown plantlets. The morphogenetic structures were not normally able to differentiate complete plants. They did show cellular proliferation with the inception of additional secondary embryos, leaf-like structures and unorganized masses of callus. Nevertheless, some ectopic structures isolated from roots and transferred onto fresh basal medium without growth regulators were able to produce plantlets that exhibited the same phenotype as the original clone. Histological analyses demonstrate that they originate from cortical cells in association with the development of lateral root primordia.
NEUROTOXIC (+)-METHAMPHETAMINE TREATMENT INCREASES BRAIN-DERIVED NEUROTROPHIC FACTOR AND TROPOMYOSIN RECEPTOR KINASE B (TrkB) EXPRESSION IN MULTIPLE BRAIN REGIONS

Methamphetamine (MA) is an abused stimulant which can result in cognitive deficits and monoamine depletions. Animal models of neurotoxic MA exposure show reductions in dopamine, serotonin, and their associated transporters. MA abuse can result in long-term attention, working memory, and executive function deficits in humans and deficits in route-based egocentric learning, novel object recognition, and novel odor preference in rodents. MA has also been shown to affect brain-derived neurotrophic factor (BDNF) in humans and rodents. This experiment examined the effects of a MA binge dosing regimen (10 mg/kg × 4 at 2 h intervals, s.c.) in Sprague-Dawley rats on BDNF, tropomyosin receptor kinase B (TrkB), and tyrosine hydroxylase (TH) mRNA expression, and plasma corticosterone. Tissues were collected 1, 7, and 24 h following the last MA dose. Expression of BDNF and TrkB mRNA was analyzed using in situ hybridization with cRNA probes. Frontal, parietal, and entorhinal cortical BDNF mRNA expression were increased by MA exposure at all time-points. Increases in BDNF mRNA message were also seen in the hippocampal CA1, prefrontal cortex (PFC), piriform cortex, and locus coeruleus but only at specific times. TrkB mRNA expression was modified in several subregions of the hippocampus as well as in PFC and striatum. TH mRNA was increased at the 1 h time-point in the substantia nigra pars compacta with no differences noted at the other times. Corticosterone levels were increased at all three timepoints. The findings suggest that BDNF and its receptor may be upregulated as a compensatory mechanism after MA exposure. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved. *Correspondence: Michael T. Williams, PhD or Charles V. Vorhees, PhD, Cincinnati Children’s Research Foundation, Division of Neurology (MLC 7044), 3333 Burnet Ave., Cincinnati OH 45229, Tel. (513) 636-8624 (mtw); (513) 636-8622 (cvv), Fax (513) 636-3912, Michael.Williams@cchmc.org or Charles.Vorhees@cchmc.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author Manuscript Neuroscience. Author manuscript; available in PMC 2012 June 16. Published in final edited form as: Neuroscience. 2011 June 16; 184: 164–171. doi:10.1016/j.neuroscience. 2011.03. 045. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript
implications and potential prognostic and predictive biomarkers of the PI3K-Akt-mTOR signaling pathway. Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathway in non-small cell lung cancer

: Non-small cell lung cancer (NSCLC) is a devastating disease with poor prognosis. Systemic chemotherapy has been the mainstay of treatment in advanced disease for many decades. Personalized targeted therapy such as epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) and crizotinib has significantly changed the treatment paradigm in NSCLC. The future success of development of molecular targeted therapy relies on the understanding of signal transduction pathways. The PI3K-Akt-mTOR pathway is commonly deregulated in human malignancy including NSCLC. Therefore, this pathway is a target for many therapeutic developments. This review will provide an overview of PI3K-Akt-mTOR signaling pathway, genetic alterations activating the pathway and clinical therapeutic development of pathway inhibitors. ligand and expression of p27Kip1 and retinobloastoma-like 2 (RBL2) causing cell cycle arrest (20). There are a number of review articles that have elegantly illustrated and described this complex network of downstream substrates of Akt (7,8,10,14).
A Novel Donor Splice Site in Intron I I of the CFTR Gene, Created by Mutation

mRNA analysis of the cystic fibrosis transmembrane regulator (CFTR) gene in tissues of cystic fibrosis (CF) patients has allowed us to detect a cryptic exon. The new exon involves 49 base pairs between exons 11 and 12 and is due to a point mutation (1811+1.6kbA-+G) that creates a new donor splice site in intron 11. Semiquantitative mRNA analysis showed that 1811+1.6kbA--G-mRNA was 5-10-fold less abundant than AF508 mRNA. Mutation 1811+1.6kbA-+G was found in 21 Spanish and 1 German CF chromosomes, making it the fourth-most-frequent mutation (2%) in the Spanish population. Individuals with genotype AF508/1811+1.6kbA--G have only 1%-3% of normal CFTR mRNA. This loss of 97% of normal CFTR mRNA must be responsible for the pancreatic insufficiency and for the severe CF phenotype in these patients.
Valproic Acid Induced Fetal Malformations Are Reduced by Maternal Immune Stimulation with Granulocyte-Macrophage Colony-Stimulating Factor or Interferon γ

Valproic acid, a drug commonly used to treat seizures and other psychiatric disorders, causes neural tube defects (NTDs) in exposed fetuses at a rate 20 times higher than in the general population. Failure of the neural tube to close during development, results in exencephaly or anencephaly, and spina bifida. In mice, non specific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes induced NTDs. We hypothesized that nonspecific activation of the maternal immune system with IFN γ and GM-CSF could reduce valproic acid (VA) induced defects as well. Female CD-1 mice were given immune stimulant pre-breeding; either IFN γ or GM-CSF. Approximately half of the control and immune stimulated pregnant females were then exposed to 500 mg/kg VA on the morning of gestational day 8. The incidence of developmental defects was determined on gestational day 17 from at least 8 litters in each of the following treatment groups: Control, VA only, IFN γ only, IFN γ +VA, GM-CSF only, GM-CSF+VA. NTDs were significantly reduced from 18% in VA exposed fetuses to 3.7% in IFN γ +VA, and 2.9% in GM-CSF+VA treatment groups. Ocular defects were also significantly reduced from 28.0% in VA exposed groups to 9.8% in IFN γ +VA and 12.5% in GM-CSF+VA groups. The mechanisms responsible for the reduction in birth defects by maternal immune stimulation remain unclear, but may involve maternal or fetal production of cytokines or growth factors which protect the fetus from the dysregulatory effects of teratogens.
UvA-DARE ( Digital Academic Repository ) Language Models for Searching in Web

We describe our participation in the TREC 2004 Web and Terabyte tracks. For the web track, we employ mixture language models based on document full-text, incoming anchortext, and documents titles, with a range of webcentric priors. We provide a detailed analysis of the effect on relevance of document length, URL structure, and link topology. The resulting web-centric priors are applied to three types of topics—distillation, home page, and named page—and improve effectiveness for all topic types, as well as for the mixed query set. For the terabyte track, we experimented with building an index just based on the document titles, or on the incoming anchor texts. Very selective indexing leads to a compact index that is effective in terms of early precision, catering for the typical web searcher behavior.
PGE 2 DEPRESSES SOLITARY TRACT-MEDIATED SYNAPTIC TRANSMISSION IN THE NTS

Prostaglandin E 2 (PGE 2 ) is a prototypical inflammatory mediator that excites and sensitizes cell bodies (Kwong and Lee, 2002; 2005) and peripheral nerve terminals (Ho et al. 2000) of primary vagal sensory neurons. Nearly all central nerve terminals of vagal afferents are in the nucleus tractus solitarius (NTS), where they operate with a high probability of release (Doyle and Andresen, 2001). We studied the effect of PGE 2 on synaptic transmission between tractus solitarius afferent nerve terminals and the second order NTS neurons in brain stem slices of Sprague Dawley rats. Whole-cell patch recording in voltage clamp mode was used to study evoked excitatory postsynaptic glutamatergic currents (evEPSCs) from NTS neurons elicited by electrical stimulation of the solitary tract (ST). In 34 neurons, bath applied PGE 2 (200 nM) decreased the evEPSC amplitude by 49 ± 5 %. In 22 neurons, however, PGE 2 had no effect. We also tested 15 NTS neurons for capsaicin sensitivity. Seven neurons generated evEPSCs that were equally unaffected by PGE 2 and capsaicin. Conversely, evEPSCs of the other 8 neurons, which were PGE 2 -responsive, were abolished by 200 nM capsaicin. Furthermore, the PGE 2- induced depression of evEPSCs was associated with an increase in the paired pulse ratio and a decrease in both the frequency and amplitude of the spontaneous excitatory postsynaptic currents (sEPSCs) and TTX-independent spontaneous miniature excitatory postsynaptic currents (mEPSCs). These results suggest that PGE 2 acts both presynaptically on nerve terminals and postsynaptically on NTS neurons to reduce glutamatergic responses. of the peripheral actions of PGE 2 . However, our results indicate that the majority of central vagal synapses were by PGE 2 In NTS neurons tested,
Behavioral Weight Control Treatment Combined with Supervised Exercise or Peer Enhanced Adventure for Overweight Adolescents

Objectives— To evaluate the efficacy of behavioral weight control intervention combined with a peer-enhanced activity intervention versus structured aerobic exercise in decreasing BMI and z-BMI in overweight adolescents. Study design— Participants were randomized to one of two group-based treatment conditions: 1) cognitive behavioral treatment combined with peer enhanced adventure therapy (CBT+PEAT) or 2) cognitive behavioral weight control treatment combined with supervised aerobic exercise (CBT +EXER). Participants included 118 overweight adolescents, ages 13 – 16 years, and a primary caregiver. Changes in body mass index (BMI), standardized BMI, percent over BMI, and waist circumference were examined. Results— Analysis of variance based on intent to treat (ITT) indicated significant decreases in all weight change outcomes at end of treatment, with significant decreases maintained at 12-month follow-up. No differences between treatment conditions were observed. Secondary analyses indicated that adherence with attendance and completion of weekly diet records contributed significantly to reductions in BMI. Conclusions— A cognitive behavioral weight control intervention combined with supervised aerobic exercise or peer-enhanced adventure therapy is equally effective in short-term reduction of BMI and z-BMI among overweight adolescents. Adherence, as measured by session attendance and self-monitoring, is a key dimension of weight change.
Characterization of PDHf31, the structural gene for the pyruvate dehydrogenase 13 subunit from Saccharomyces cerevisiae

The gene encoding the pyruvate dehydrogenase (PDH) ( subunit (EIB) of the PDH complex from Saccharomyces cereviswae has been cloned, sequenced, disrupted, and expressed. Two overlapping DNA fragments were generated from a yeast genomic DNA library by the polymerase chain reaction with synthetic oligonucleotide primers based on amino acid sequences of the yeast and human Ell subunits. The DNA fragments were subcloned and sequenced. The composite sequence has an open reading frame of 1098 nucleotides encoding a putative presequence of 33 amino acid residues and a mature protein of 333 residues with a calculated Mr = 36,486. Yeast and human Elfi exhibit 62% sequence identity. The size of the mRNA is -1.5 kilobases. Hybridization analysis showed that the Elp gene (PDHlI) is localized to chromosome H. Disruption of PDHfI3 is not lethal under vegetative growth conditions. The null mutant transformed with PDHfPi on a unit-copy plasmid produced mature Ell and a functional PDH complex.
Role of Growth Arrest and DNA Damage-Inducible, Beta (GADD45b) in Alcohol Drinking Behaviors

Background— The contribution of epigenetic factors, such as histone acetylation and DNA methylation, to the regulation of alcohol drinking behavior has been increasingly recognized over the last several years. GADD45b is a protein demonstrated to be involved in DNA demethylation at neurotrophic factor gene promoters, including at Brain-derived neurotrophic factor ( Bdnf ) which has been highly implicated in alcohol drinking behavior. Methods— DNA methyltransferase-1 ( Dnmt1 ), 3a , and 3b , and Gadd45a , b , and g mRNA were measured in the nucleus accumbens (NAc) and ventral tegmental areas (VTA) of high ethanol consuming C57BL/6J (C57) and low alcohol consuming DBA/2J (DBA) mice using qRT-PCR. In the NAc GADD45b protein was measured via immunohistochemistry and Bdnf9a mRNA using in situ PCR. Bdnf9a promoter histone H3 acetylated at lysines 9 and 14 (H3K9,K14ac) was measured using chromatin immunoprecipitation, and 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) using methylated DNA immunoprecipitation. Alcohol drinking behavior was evaluated in Gadd45b haplodeficient (+/−) and null mice (−/−) utilizing drinking in the dark (DID) and 2-bottle free-choice paradigms. Results— C57 mice had lower levels of Gadd45b and g mRNA and GADD45b protein in the NAc relative to the DBA strain. C57 mice had lower NAc shell Bdnf9a mRNA levels, Bdnf9a promoter H3K9,K14ac, and higher Bdnf9a promoter 5HMC and 5MC. Acute ethanol increased GADD45b protein, Bdnf9a mRNA, and histone acetylation and decreased 5HMC in C57 mice. Gadd45b +/− mice displayed higher drinking behavior relative to wild-type littermates in both DID and 2-bottle free-choice paradigms. Conclusions— These data indicate the importance of the DNA demethylation pathway and its interactions with histone post-translational modifications in alcohol drinking behavior. Further, we suggest that lower DNA demethylation protein GADD45b levels may affect Bdnf expression possibly leading to altered alcohol drinking behavior. for The are represented as the mean OD per 100 pixel area. We measured and 5MC at the Bdnf9a promoter via (hMeDIP) and DNA immunoprecipitation (MeDIP). We find that C57 mice have increased levels of 5HMC and 5MC at the Bdnf9a promoter in the NAc compared to DBA mice. One hour after an i.p. administration of ethanol 2 g/kg (EtOH) the 5HMC difference between C57 and DBA mice is no longer significant (n = 6–8 per group). B. H3K9,14ac was measured at the Bdnf9a promoter via chromatin immunoprecipitation (ChIP). We find that mice have lower levels of H3K9,14ac at the Bdnf9a promoter in the NAc compared to DBA mice. One hour after an i.p. administration of EtOH 2 g/kg H3K9,14ac levels no longer differ between C57 and DBA mice (n = 7–8 per group). Values are mean±SEMs.