Pressure-dependent studies on hydration of the C–H group in formic acid

[[abstract]]The infrared spectroscopic profiles of HCOOD/D2O mixtures were measured as a function of pressure and concentration. The C–H bond of HCOOD shortens as the pressure is elevated, while the increase in C–H bond length upon diluting HCOOD with D2O was observed. Based on the experimental results, the shift in frequency of C–H stretching band is concluded to relate to the mechanism of the hydration of the C–H group and the water structure in the vicinity of the C–H group. The pressure-dependent results can be attributed to the strengthening of C–H---O electrostatic/dispersion interaction upon increasing pressure. The observations are in accord with ab initio calculation forecasting a blueshift of the C–H stretching mode via C–H---O interaction in HCOOD-water/~HCOOD!2-~D2O! complexes relative to the noninteracting monomer/dimer. Hydrogen-bonding nonadditivity and the size of water clusters are suggested to be responsible to cause the redshift in C–H stretching mode upon dilution HCOOD with D2O.[[notice]]補正完畢[[journaltype]]國內[[booktype]]紙

Penguin-induced Radiative Baryonic B Decays Revisited

Weak radiative baryonic B decays $\bar B\to B_1\bar B_2\gamma$ mediated by the electromagnetic penguin process $b\to s\gamma$ are re-examined within the framework of the pole model. The meson pole contribution that has been neglected before is taken into account in this work. It is found that the intermediate $K^*$ contribution dominates in the $\Sigma\bar p\gamma$ mode and is comparable to the baryon pole effect in $\Lambda\bar p\gamma$ and $\Xi\bar\Lambda\gamma$ modes. The branching ratios for $B^-\to\Lambda\bar p\gamma$ and $B^-\to\Xi^0\bar\Sigma^-\gamma$ are of order $2.6\times 10^{-6}$ and $6\times 10^{-7}$, respectively. The threshold enhancement effect in the dibaryon mass spectrum is responsible by the meson pole diagram. We also study the angular distribution of the baryon in the dibaryon rest frame. The baryon pole diagrams imply that the antibaryon tends to emerge in the direction of the photon in the baryon-pair rest frame. The predicted angular asymmetry agrees with experiment for $B^-\to\Lambda\bar p\gamma$. Measurements of the correlation of the photon with the baryon allow us to discriminate between different models for describing the radiative baryonic B decays. For decays $B\to\Xi\bar\Sigma\gamma$, a large correlation of the photon to the $\bar\Sigma$ and a broad bump in the dibaryon mass spectrum are predicted.Comment: 10 pages, 4 figure

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

The sensitivity of non-small cell lung cancer (NSCLC) patients to EGFR tyrosine kinase inhibitors (TKIs) is strongly associated with activating EGFR mutations. Although not as sensitive as patients harboring these mutations, some patients with wild-type EGFR (wtEGFR) remain responsive to EGFR TKIs, suggesting that the existence of unexplored mechanisms renders most of wtEGFR-expressing cancer cells insensitive.Here, we show that acquired resistance of wtEGFR-expressing cancer cells to an EGFR TKI, gefitinib, is associated with elevated expression of breast cancer resistance protein (BCRP/ABCG2), which in turn leads to gefitinib efflux from cells. In addition, BCRP/ABCG2 expression correlates with poor response to gefitinib in both cancer cell lines and lung cancer patients with wtEGFR. Co-treatment with BCRP/ABCG2 inhibitors enhanced the anti-tumor activity of gefitinib.Thus, BCRP/ABCG2 expression may be a predictor for poor efficacy of gefitinib treatment, and targeting BCRP/ABCG2 may broaden the use of gefitinib in patients with wtEGFR

Is clopidogrel better than aspirin following breakthrough strokes while on aspirin? A retrospective cohort study.

ObjectiveThere is insufficient evidence on which to base a recommendation for optimal antiplatelet therapy following a stroke while on aspirin. The objective was to compare clopidogrel initiation vs aspirin reinitiation for vascular risk reduction among patients with ischaemic stroke on aspirin at the time of their index stroke.DesignRetrospective.SettingWe conducted a nationwide cohort study by retrieving all hospitalised patients (≥18 years) with a primary diagnosis of ischaemic stroke between 2003 and 2009 from Taiwan National Health Insurance Research Database.ParticipantsAmong 3862 patients receiving aspirin before the index ischaemic stroke and receiving either aspirin or clopidogrel after index stroke during follow-up period, 1623 were excluded due to a medication possession ratio <80%. Also, 355 were excluded due to history of atrial fibrillation, valvular heart disease or coagulopathy. Therefore, 1884 patients were included in our final analysis.InterventionsPatients were categorised into two groups based on whether clopidogrel or aspirin was prescribed during the follow-up period. Follow-up was from time of the index stroke to admission for recurrent stroke or myocardial infarction, death or the end of 2010.Primary and secondary outcome measuresThe primary end point was hospitalisation due to a new-onset major adverse cardiovascular event (MACE: composite of any stroke or myocardial infarction). The leading secondary end point was any recurrent stroke.ResultsCompared to aspirin, clopidogrel was associated with a lower occurrence of future MACE (HR=0.54, 95% CI 0.43 to 0.68, p<0.001, number needed to treat: 8) and recurrent stroke (HR=0.54, 95% CI 0.42 to 0.69, p<0.001, number needed to treat: 9) after adjustment of relevant covariates.ConclusionsAmong patients with an ischaemic stroke while taking aspirin, clopidogrel initiation was associated with fewer recurrent vascular events than aspirin reinitiation

IKKβ Suppression of TSC1 Links Inflammation and Tumor Angiogenesis via the mTOR Pathway

SummaryTNFα has recently emerged as a regulator linking inflammation to cancer pathogenesis, but the detailed cellular and molecular mechanisms underlying this link remain to be elucidated. The tuberous sclerosis 1 (TSC1)/TSC2 tumor suppressor complex serves as a repressor of the mTOR pathway, and disruption of TSC1/TSC2 complex function may contribute to tumorigenesis. Here we show that IKKβ, a major downstream kinase in the TNFα signaling pathway, physically interacts with and phosphorylates TSC1 at Ser487 and Ser511, resulting in suppression of TSC1. The IKKβ-mediated TSC1 suppression activates the mTOR pathway, enhances angiogenesis, and results in tumor development. We further find that expression of activated IKKβ is associated with TSC1 Ser511 phosphorylation and VEGF production in multiple tumor types and correlates with poor clinical outcome of breast cancer patients. Our findings identify a pathway that is critical for inflammation-mediated tumor angiogenesis and may provide a target for clinical intervention in human cancer

Charmless Exclusive Baryonic B Decays

We present a systematical study of two-body and three-body charmless baryonic B decays. Branching ratios for two-body modes are in general very small, typically less than $10^{-6}$, except that \B(B^-\to p \bar\Delta^{--})\sim 1\times 10^{-6}. In general, $\bar B\to N\bar\Delta>\bar B\to N\bar N$ due to the large coupling constant for $\Sigma_b\to B\Delta$. For three-body modes we focus on octet baryon final states. The leading three-dominated modes are $\bar B^0\to p\bar n\pi^-(\rho^-), n\bar p\pi^+(\rho^+)$ with a branching ratio of order $3\times 10^{-6}$ for $\bar B^0\to p\bar n\pi^-$ and $8\times 10^{-6}$ for $\bar B^0\to p\bar n\rho^-$. The penguin-dominated decays with strangeness in the meson, e.g., $B^-\to p\bar p K^{-(*)}$ and $\bar B^0\to p\bar n K^{-(*)}, n\bar n \bar K^{0(*)}$, have appreciable rates and the $N\bar N$ mass spectrum peaks at low mass. The penguin-dominated modes containing a strange baryon, e.g., $\bar B^0\to \Sigma^0\bar p\pi^+, \Sigma^-\bar n\pi^+$, have branching ratios of order $(1\sim 4)\times 10^{-6}$. In contrast, the decay rate of $\bar B^0\to\Lambda\bar p\pi^+$ is smaller. We explain why some of charmless three-body final states in which baryon-antibaryon pair production is accompanied by a meson have a larger rate than their two-body counterparts: either the pole diagrams for the former have an anti-triplet bottom baryon intermediate state, which has a large coupling to the $B$ meson and the nucleon, or they are dominated by the factorizable external $W$-emission process.Comment: 46 pages and 3 figures, to appear in Phys. Rev. D. Major changes are: (i) Calculations of two-body baryonic B decays involving a Delta resonance are modified, and (ii) Penguin-dominated modes B-> Sigma+N(bar)+p are discusse

bZIP-Type transcription factors CREB and OASIS bind and stimulate the promoter of the mammalian transcription factor GCMa/Gcm1 in trophoblast cells

One of the master regulators of placental cell fusion in mammals leading to multi-nucleated syncytiotrophoblasts is the transcription factor GCMa. Recently, we proved that the cAMP-driven protein kinase A signaling pathway is fundamental for up-regulation of GCMa transcript levels and protein stability. Here, we show that Transducer of Regulated CREB activity (TORC1), the human co-activator of cAMP response element-binding protein (CREB), but not a dominant-negative CREB mutant, significantly up-regulates the GCMa promoter. We identified potential cAMP response element (CRE)-binding sites within the GCMa promoter upstream of the transcriptional start site. Only the CRE site at -1337 interacted strongly with CREB in promoter mapping experiments. The characterization of GCMa promoter mutants and additional bZIP-type family members demonstrated that also old astrocyte specifically-induced substance (OASIS) is able to stimulate GCMa transcription. Knockdown of endogenous CREB or OASIS in BeWo cells decreased endogenous GCMa mRNA level and activity. Overexpression of TORC1 or OASIS in choriocarcinoma cells led to placental cell fusion, accompanied by placental expression of gap junction forming protein connexin-43. Further, we show that CREB expression is replaced by OASIS expression around E12.5 suggesting that a sequential order of bZIP-type family members ensures a high rate of GCMa transcription throughout placentation

Genome-Wide Gene Expression Analysis Implicates the Immune Response and Lymphangiogenesis in the Pathogenesis of Fetal Chylothorax

Fetal chylothorax (FC) is a rare condition characterized by lymphocyte-rich pleural effusion. Although its pathogenesis remains elusive, it may involve inflammation, since there are increased concentrations of proinflammatory mediators in pleural fluids. Only a few hereditary lymphedema-associated gene loci, e.g. VEGFR3, ITGA9 and PTPN11, were detected in human fetuses with this condition; these cases had a poorer prognosis, due to defective lymphangiogenesis. In the present study, genome-wide gene expression analysis was conducted, comparing pleural and ascitic fluids in three hydropic fetuses, one with and two without the ITGA9 mutation. One fetus (the index case), from a dizygotic pregnancy (the cotwin was unaffected), received antenatal OK-432 pleurodesis and survived beyond the neonatal stage, despite having the ITGA9 mutation. Genes and pathways involved in the immune response were universally up-regulated in fetal pleural fluids compared to those in ascitic fluids. Furthermore, genes involved in the lymphangiogenesis pathway were down-regulated in fetal pleural fluids (compared to ascitic fluid), but following OK-432 pleurodesis, they were up-regulated. Expression of ITGA9 was concordant with overall trends of lymphangiogenesis. In conclusion, we inferred that both the immune response and lymphangiogenesis were implicated in the pathogenesis of fetal chylothorax. Furthermore, genome-wide gene expression microarray analysis may facilitate personalized medicine by selecting the most appropriate treatment, according to the specific circumstances of the patient, for this rare, but heterogeneous disease

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Genome-Wide Association Study of Treatment Refractory Schizophrenia in Han Chinese

We report the first genome-wide association study of a joint analysis using 795 Han Chinese individuals with treatment-refractory schizophrenia (TRS) and 806 controls. Three loci showed suggestive significant association with TRS were identified. These loci include: rs10218843 (P = 3.04×10−7) and rs11265461 (P = 1.94×10−7) are adjacent to signaling lymphocytic activation molecule family member 1 (SLAMF1); rs4699030 (P = 1.94×10−6) and rs230529 (P = 1.74×10−7) are located in the gene nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1); and rs13049286 (P = 3.05×10−5) and rs3827219 (P = 1.66×10−5) fall in receptor-interacting serine/threonine-protein kinase 4 (RIPK4). One isolated single nucleotide polymorphism (SNP), rs739617 (P = 3.87×10−5) was also identified to be associated with TRS. The -94delATTG allele (rs28362691) located in the promoter region of NFKB1 was identified by resequencing and was found to associate with TRS (P = 4.85×10−6). The promoter assay demonstrated that the -94delATTG allele had a significant lower promoter activity than the -94insATTG allele in the SH-SY5Y cells. This study suggests that rs28362691 in NFKB1 might be involved in the development of TRS